Special Issue "Mitochondria in Health and Diseases"

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Organelle Function".

Deadline for manuscript submissions: closed (15 December 2019).

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Prof. Sabzali Javadov
Website
Guest Editor
Department of Physiology, University of Puerto Rico School of Medicine, San Juan, Puerto Rico, USA
Interests: cell death; mitochondria; mitochondrial permeability transition; ETC supercomplexes; mitochondrial ROS; cardiac ischemia–reperfusion; myocardial infarction; mitochondria-targeted cardioprotection
Prof. Dr. Andrey V. Kozlov
Website
Guest Editor
Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Vienna, Austria
Interests: mitochondrial ROS; mitochondrial ROS signaling; TCA cycle; pyruvate dehydrogenase complex; oxoglutarate dehydrogenase complex; shock; inflammation; traumatic brain injury
Special Issues and Collections in MDPI journals
Prof. Amadou K.S. Camara
Website
Guest Editor
Department of Anesthesiology and Anesthesia Research, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
Interests: mitochondria; mitochondrial calcium regulation; voltage dependent anion channel; hexokinase; adenine nucleotide translocator; ischemia and reperfusion; reactive oxygen and nitrogen species; hypothermia; traumatic brain injury
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

Mitochondria are the “power plants” of cells due to their ability to generate ATP. In addition, mitochondria play an important role in other aspects of cell metabolism and function, including ion homeostasis, cell growth, redox signaling, and cell survival. The structural and functional integrity of mitochondria is maintained by mitochondrial quality control through mitochondrial biogenesis (turnover), dynamics (fission and fusion), and selective mitophagy. Notably, the structural organization and dynamics of mitochondria vary greatly between organ and tissues to meet tissue-specific cellular needs. Mitochondria are also involved in the pathogenesis and progression of numerous human diseases including, among others, cancer, neurodegenerative and cardiovascular diseases, diabetes, traumatic injury, and inflammation. Mitochondrial involvement in these diseases has been attributed to the central role the organelle plays in the sequelae of events that culminate in cell death through various mechanisms such as apoptosis, necrosis, and autophagy. More recently, it has been shown that also ferroptosis is associated with atypical mitochondrial morphology. Despite the intense focus on the role of mitochondria, the precise niche the organelle play in cell life and death remains unknown. Lack of in-depth knowledge of the regulatory mechanisms of mitochondrial metabolism and the function and interplay between the factors that transform the organelle from cell preservation to cell death compromise the development of new mitochondria-targeted approaches to treat human diseases.

This Special Issue of Cells is designed to highlight all aspects of mitochondrial metabolism and to function under physiological and pathological conditions. We will consider high-quality articles on mitochondrial biology as well as on the role of mitochondria in disease and aging. The Special Issue welcomes studies in the field of mitochondrial research using various cell and animal models, human diseases, and computational modeling. We also welcome studies that describe the application/adaptation of new methodologies and approaches in mitochondrial research.

Prof. Sabzali Javadov
Prof. Andrey V. Kozlov
Prof. Amadou K.S. Camara
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Apoptosis
  • autophagy
  • Barth syndrome
  • cardiolipin
  • cellular stress responses
  • ER-mitochondria interactions
  • Huntington disease
  • mitochondria
  • mitochondria associated membranes
  • mitochondrial biogenesis
  • mitochondrial metabolism
  • mitochondrial replication
  • mitochondrial gene expression
  • mitochondrial cell death
  • mitochondrial ion channels/exchangers
  • mitochondrial signaling
  • mitochondrial membrane transporters
  • mitochondrial respiration
  • mitochondrial permeability transition
  • mitochondrial protein synthesis
  • mitochondrial ROS
  • mitochondria-targeted therapy
  • mitochondrial sirtuins
  • mitochondrial supercomplexes
  • mitophagy
  • necrosis
  • OXPHOS
  • TCA

Published Papers (25 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Editorial

Jump to: Research, Review

Open AccessEditorial
Mitochondria in Health and Diseases
Cells 2020, 9(5), 1177; https://doi.org/10.3390/cells9051177 - 09 May 2020
Cited by 7 | Viewed by 1180
Abstract
Mitochondria are subcellular organelles evolved by endosymbiosis of bacteria with eukaryotic cells characteristics. They are the main source of ATP in the cell and play a pivotal role in cell life and cell death. Mitochondria are engaged in the pathogenesis of human diseases [...] Read more.
Mitochondria are subcellular organelles evolved by endosymbiosis of bacteria with eukaryotic cells characteristics. They are the main source of ATP in the cell and play a pivotal role in cell life and cell death. Mitochondria are engaged in the pathogenesis of human diseases and aging directly or indirectly through a broad range of signaling pathways. However, despite an increased interest in mitochondria over the past decades, the mechanisms of mitochondria-mediated cell/organ dysfunction in response to pathological stimuli remain unknown. The Special Issue, “Mitochondria in Health and Diseases,” organized by Cells includes 24 review and original articles that highlight the latest achievements in elucidating the role of mitochondria under physiological (healthy) conditions and, in various cell/animal models of human diseases and, in patients. Altogether, the Special Issue summarizes and discusses different aspects of mitochondrial metabolism and function that open new avenues in understanding mitochondrial biology. Full article
(This article belongs to the Special Issue Mitochondria in Health and Diseases) Printed Edition available
Show Figures

Figure 1

Research

Jump to: Editorial, Review

Open AccessArticle
Mitochondria in the Nuclei of Rat Myocardial Cells
Cells 2020, 9(3), 712; https://doi.org/10.3390/cells9030712 - 14 Mar 2020
Cited by 1 | Viewed by 1050
Abstract
Electron microscopic study of cardiomyocytes taken from healthy Wistar and OXYS rats and naked mole rats (Heterocephalus glaber) revealed mitochondria in nuclei that lacked part of the nuclear envelope. The direct interaction of mitochondria with nucleoplasm is shown. The statistical analysis [...] Read more.
Electron microscopic study of cardiomyocytes taken from healthy Wistar and OXYS rats and naked mole rats (Heterocephalus glaber) revealed mitochondria in nuclei that lacked part of the nuclear envelope. The direct interaction of mitochondria with nucleoplasm is shown. The statistical analysis of the occurrence of mitochondria in cardiomyocyte nuclei showed that the percentage of nuclei with mitochondria was roughly around 1%, and did not show age and species dependency. Confocal microscopy of normal rat cardiac myocytes revealed a branched mitochondrial network in the vicinity of nuclei with an organization different than that of interfibrillar mitochondria. This mitochondrial network was energetically functional because it carried the membrane potential that responded by oscillatory mode after photodynamic challenge. We suggest that the presence of functional mitochondria in the nucleus is not only a consequence of certain pathologies but rather represents a normal biological phenomenon involved in mitochondrial/nuclear interactions. Full article
(This article belongs to the Special Issue Mitochondria in Health and Diseases) Printed Edition available
Show Figures

Figure 1

Open AccessArticle
Fatty Acid Oxidation and Mitochondrial Morphology Changes as Key Modulators of the Affinity for ADP in Rat Heart Mitochondria
Cells 2020, 9(2), 340; https://doi.org/10.3390/cells9020340 - 01 Feb 2020
Cited by 1 | Viewed by 1026
Abstract
Fatty acids are the main respiratory substrates important for cardiac function, and their oxidation is altered during various chronic disorders. We investigated the mechanism of fatty acid–oxidation-induced changes and their relations with mitochondrial morphology and ADP/ATP carrier conformation on the kinetics of the [...] Read more.
Fatty acids are the main respiratory substrates important for cardiac function, and their oxidation is altered during various chronic disorders. We investigated the mechanism of fatty acid–oxidation-induced changes and their relations with mitochondrial morphology and ADP/ATP carrier conformation on the kinetics of the regulation of mitochondrial respiration in rat skinned cardiac fibers. Saturated and unsaturated, activated and not activated, long and medium chain, fatty acids similarly decreased the apparent KmADP. Addition of 5% dextran T-70 to mimic the oncotic pressure of the cellular cytoplasm markedly increased the low apparent KmADP value of mitochondria in cardiac fibers respiring on palmitoyl-l-carnitine or octanoyl-l-carnitine, but did not affect the high apparent KmADP of mitochondria respiring on pyruvate and malate. Electron microscopy revealed that palmitoyl-l-carnitine oxidation-induced changes in the mitochondrial ultrastructure (preventable by dextran) are similar to those induced by carboxyatractyloside. Our data suggest that a fatty acid oxidation-induced conformational change of the adenosine diphosphate (ADP)/adenosine triphosphate (ATP) carrier (M-state to C-state, condensed to orthodox mitochondria) may affect the oxidative phosphorylation affinity for ADP. Full article
(This article belongs to the Special Issue Mitochondria in Health and Diseases) Printed Edition available
Show Figures

Figure 1

Open AccessArticle
PPARγ-Independent Side Effects of Thiazolidinediones on Mitochondrial Redox State in Rat Isolated Hearts
Cells 2020, 9(1), 252; https://doi.org/10.3390/cells9010252 - 20 Jan 2020
Cited by 2 | Viewed by 821
Abstract
The effect of anti-diabetic thiazolidinediones (TZDs) on contributing to heart failure and cardiac ischemia/reperfusion (IR) injury is controversial. In this study we investigated the effect of select TZDs on myocardial and mitochondrial function in Brown Norway rat isolated hearts. In a first set [...] Read more.
The effect of anti-diabetic thiazolidinediones (TZDs) on contributing to heart failure and cardiac ischemia/reperfusion (IR) injury is controversial. In this study we investigated the effect of select TZDs on myocardial and mitochondrial function in Brown Norway rat isolated hearts. In a first set of experiments, the TZD rosiglitazone was given acutely before global myocardial IR, and pre- and post-IR function and infarct size were assessed. In a second set of experiments, different concentrations of rosiglitazone and pioglitazone were administered in the presence or absence of the specific PPARγ antagonist GW9662, and their effects on the mitochondrial redox state were measured by online NADH and FAD autofluorescence. The administration of rosiglitazone did not significantly affect myocardial function except for transiently increasing coronary flow, but it increased IR injury compared to the control hearts. Both TZDs resulted in dose-dependent, reversible increases in mitochondrial oxidation which was not attenuated by GW9662. Taken together, these data suggest that TZDs cause excessive mitochondrial uncoupling by a PPARγ-independent mechanism. Acute rosiglitazone administration before IR was associated with enhanced cardiac injury. If translated clinically, susceptible patients on PPARγ agonists may experience enhanced myocardial IR injury by mitochondrial dysfunction. Full article
(This article belongs to the Special Issue Mitochondria in Health and Diseases) Printed Edition available
Show Figures

Figure 1

Open AccessArticle
Hypoxic Adaptation of Mitochondrial Metabolism in Rat Cerebellum Decreases in Pregnancy
Cells 2020, 9(1), 139; https://doi.org/10.3390/cells9010139 - 07 Jan 2020
Cited by 2 | Viewed by 948
Abstract
Function of brain amino acids as neurotransmitters or their precursors implies changes in the amino acid levels and/or metabolism in response to physiological and environmental challenges. Modelling such challenges by pregnancy and/or hypoxia, we characterize the amino acid pool in the rat cerebellum, [...] Read more.
Function of brain amino acids as neurotransmitters or their precursors implies changes in the amino acid levels and/or metabolism in response to physiological and environmental challenges. Modelling such challenges by pregnancy and/or hypoxia, we characterize the amino acid pool in the rat cerebellum, quantifying the levels and correlations of 15 amino acids and activity of 2-oxoglutarate dehydrogenase complex (OGDHC). The parameters are systemic indicators of metabolism because OGDHC limits the flux through mitochondrial TCA cycle, where amino acids are degraded and their precursors synthesized. Compared to non-pregnant state, pregnancy increases the cerebellar content of glutamate and tryptophan, decreasing interdependence between the quantified components of amino acid metabolism. In response to hypoxia, the dependence of cerebellar amino acid pool on OGDHC and the average levels of arginine, glutamate, lysine, methionine, serine, phenylalanine, and tryptophan increase in non-pregnant rats only. This is accompanied by a higher hypoxic resistance of the non-pregnant vs. pregnant rats, pointing to adaptive significance of the hypoxia-induced changes in the cerebellar amino acid metabolism. These adaptive mechanisms are not effective in the pregnancy-changed metabolic network. Thus, the cerebellar amino acid levels and OGDHC activity provide sensitive markers of the physiology-dependent organization of metabolic network and its stress adaptations. Full article
(This article belongs to the Special Issue Mitochondria in Health and Diseases) Printed Edition available
Show Figures

Graphical abstract

Open AccessCommunication
Critical Impact of Human Amniotic Membrane Tension on Mitochondrial Function and Cell Viability In Vitro
Cells 2019, 8(12), 1641; https://doi.org/10.3390/cells8121641 - 15 Dec 2019
Cited by 3 | Viewed by 813
Abstract
Amniotic cells show exciting stem cell features, which has led to the idea of using living cells of human amniotic membranes (hAMs) in toto for clinical applications. However, under common cell culture conditions, viability of amniotic cells decreases rapidly, whereby reasons for this [...] Read more.
Amniotic cells show exciting stem cell features, which has led to the idea of using living cells of human amniotic membranes (hAMs) in toto for clinical applications. However, under common cell culture conditions, viability of amniotic cells decreases rapidly, whereby reasons for this decrease are unknown so far. Recently, it has been suggested that loss of tissue tension in vivo leads to apoptosis. Therefore, the aim of this study was to investigate the effect of tissue distention on the viability of amniotic cells in vitro. Thereby, particular focus was put on vital mitochondria-linked parameters, such as respiration and ATP synthesis. Biopsies of hAMs were incubated for 7–21 days either non-distended or distended. We observed increased B-cell lymphoma 2-associated X protein (BAX)/B-cell lymphoma (BCL)-2 ratios in non-distended hAMs at day seven, followed by increased caspase 3 expression at day 14, and, consequently, loss of viability at day 21. In contrast, under distention, caspase 3 expression increased only slightly, and mitochondrial function and cellular viability were largely maintained. Our data suggest that a mechano-sensing pathway may control viability of hAM cells by triggering mitochondria-mediated apoptosis upon loss of tension in vitro. Further studies are required to elucidate the underlying molecular mechanisms between tissue distention and viability of hAM cells. Full article
(This article belongs to the Special Issue Mitochondria in Health and Diseases) Printed Edition available
Show Figures

Figure 1

Open AccessArticle
Mitochondrial DNA Variation of Leber’s Hereditary Optic Neuropathy in Western Siberia
Cells 2019, 8(12), 1574; https://doi.org/10.3390/cells8121574 - 04 Dec 2019
Cited by 2 | Viewed by 890
Abstract
Our data first represent the variety of Leber’s hereditary optic neuropathy (LHON) mutations in Western Siberia. LHON is a disorder caused by pathogenic mutations in the mitochondrial DNA (mtDNA), inherited maternally and presents mainly in young adults, predominantly males. Clinically, LHON manifests itself [...] Read more.
Our data first represent the variety of Leber’s hereditary optic neuropathy (LHON) mutations in Western Siberia. LHON is a disorder caused by pathogenic mutations in the mitochondrial DNA (mtDNA), inherited maternally and presents mainly in young adults, predominantly males. Clinically, LHON manifests itself as painless central vision loss, resulting in early onset of disability. The epidemiology of LHON has not been fully investigated yet. In this study, we report 44 genetically unrelated families with LHON manifestation. We performed whole mtDNA genome sequencing and provided genealogical and molecular genetic data on mutations and haplogroup background of LHON patients. Known “primary” pathogenic mtDNA mutations (MITOMAP) were found in 32 families: m.11778G>A represents 53.10% (17/32), m.3460G>A—21.90% (7/32), m.14484T>C–18.75% (6/32), and rare m.10663T>C and m.3635G>A represent 6.25% (2/32). We describe potentially pathogenic m.4659G>A in one subject without known pathogenic mutations, and potentially pathogenic m.6261G>A, m.8412T>C, m.8551T>C, m.9444C>T, m.9921G>A, and m.15077G>A in families with known pathogenic mutations confirmed. We suppose these mutations could contribute to the pathogenesis of optic neuropathy development. Our results indicate that haplogroup affiliation and mutational spectrum of the Western Siberian LHON cohort substantially deviate from those of European populations. Full article
(This article belongs to the Special Issue Mitochondria in Health and Diseases) Printed Edition available
Show Figures

Figure 1

Open AccessArticle
Advanced Age Is Associated with Iron Dyshomeostasis and Mitochondrial DNA Damage in Human Skeletal Muscle
Cells 2019, 8(12), 1525; https://doi.org/10.3390/cells8121525 - 27 Nov 2019
Cited by 11 | Viewed by 1239
Abstract
Whether disruption of iron metabolism is implicated in human muscle aging is presently unclear. We explored the relationship among iron metabolism, muscle mitochondrial homeostasis, inflammation, and physical function in older adults and young controls. Eleven young and 23 older men and women were [...] Read more.
Whether disruption of iron metabolism is implicated in human muscle aging is presently unclear. We explored the relationship among iron metabolism, muscle mitochondrial homeostasis, inflammation, and physical function in older adults and young controls. Eleven young and 23 older men and women were included. Older adults were classified into high–functioning (HF) and low–functioning (LF) groups according to their Short Physical Performance Battery score. Vastus lateralis muscle biopsies were assayed for total iron content, expression of 8-oxoguanine and DNA glycosylase (OGG1), 3-nitrotyrosine (3-NT) levels, and mitochondrial DNA (mtDNA) content and damage. Circulating ferritin and hepcidin levels were also quantified. Muscle iron levels were greater in the old group. Protein expression of transferrin receptor 1, Zrt-Irt-like protein (ZIP) 8, and ZIP14 were lower in old participants. Circulating levels of ferritin, hepcidin, interleukin 6 (IL6), and C-reactive protein were higher in the old group. Old participants showed lower mtDNA content and greater mtDNA damage. OGG1 protein expression declined with age, whereas 3-NT levels were greater in old participants. Finally, a negative correlation was determined between ZIP14 expression and circulating IL6 levels in LF older adults. None of assayed parameters differed between HF and LF participants. Our findings suggest that muscle iron homeostasis is altered in old age, which might contribute to loss of mtDNA stability. Muscle iron metabolism may therefore represent a target for interventions against muscle aging. Full article
(This article belongs to the Special Issue Mitochondria in Health and Diseases) Printed Edition available
Show Figures

Figure 1

Open AccessArticle
TRPC6-Mediated ERK1/2 Activation Increases Dentate Granule Cell Resistance to Status Epilepticus via Regulating Lon Protease-1 Expression and Mitochondrial Dynamics
Cells 2019, 8(11), 1376; https://doi.org/10.3390/cells8111376 - 01 Nov 2019
Cited by 4 | Viewed by 1123
Abstract
Transient receptor potential canonical channel-6 (TRPC6) is one of the Ca2+-permeable non-selective cation channels. TRPC6 is mainly expressed in dentate granule cell (DGC), which is one of the most resistant neuronal populations to various harmful stresses. Although TRPC6 knockdown evokes the [...] Read more.
Transient receptor potential canonical channel-6 (TRPC6) is one of the Ca2+-permeable non-selective cation channels. TRPC6 is mainly expressed in dentate granule cell (DGC), which is one of the most resistant neuronal populations to various harmful stresses. Although TRPC6 knockdown evokes the massive DGC degeneration induced by status epilepticus (a prolonged seizure activity, SE), the molecular mechanisms underlying the role of TRPC6 in DGC viability in response to SE are still unclear. In the present study, hyperforin (a TRPC6 activator) facilitated mitochondrial fission in DGC concomitant with increases in Lon protease-1 (LONP1, a mitochondrial protease) expression and extracellular-signal-regulated kinase 1/2 (ERK1/2) phosphorylation under physiological conditions, which were abrogated by U0126 (an ERK1/2 inhibitor) co-treatment. TRPC6 knockdown showed the opposite effects on LONP1 expression, ERK1/2 activity, and mitochondrial dynamics. In addition, TRPC6 siRNA and U0126 evoked the massive DGC degeneration accompanied by mitochondrial elongation following SE, independent of seizure severity. However, LONP1 siRNA exacerbated SE-induced DGC death without affecting mitochondrial length. These findings indicate that TRPC6-ERK1/2 activation may increase DGC invulnerability to SE by regulating LONP1 expression as well as mitochondrial dynamics. Therefore, TRPC6-ERK1/2-LONP1 signaling pathway will be an interesting and important therapeutic target for neuroprotection from various neurological diseases. Full article
(This article belongs to the Special Issue Mitochondria in Health and Diseases) Printed Edition available
Show Figures

Graphical abstract

Open AccessArticle
The Role of Adenine Nucleotide Translocase in the Assembly of Respiratory Supercomplexes in Cardiac Cells
Cells 2019, 8(10), 1247; https://doi.org/10.3390/cells8101247 - 13 Oct 2019
Cited by 5 | Viewed by 1052
Abstract
Individual electron transport chain complexes have been shown to assemble into the supramolecular structures known as the respiratory chain supercomplexes (RCS). Several studies reported an associative link between RCS disintegration and human diseases, although the physiological role, structural integrity, and mechanisms of RCS [...] Read more.
Individual electron transport chain complexes have been shown to assemble into the supramolecular structures known as the respiratory chain supercomplexes (RCS). Several studies reported an associative link between RCS disintegration and human diseases, although the physiological role, structural integrity, and mechanisms of RCS formation remain unknown. Our previous studies suggested that the adenine nucleotide translocase (ANT), the most abundant protein of the inner mitochondrial membrane, can be involved in RCS assembly. In this study, we sought to elucidate whether ANT knockdown (KD) affects RCS formation in H9c2 cardiomyoblasts. Results showed that genetic silencing of ANT1, the main ANT isoform in cardiac cells, stimulated proliferation of H9c2 cardiomyoblasts with no effect on cell viability. ANT1 KD reduced the ΔΨm but increased total cellular ATP levels and stimulated the production of total, but not mitochondrial, reactive oxygen species. Importantly, downregulation of ANT1 had no significant effects on the enzymatic activity of individual ETC complexes I–IV; however, RCS disintegration was stimulated in ANT1 KD cells as evidenced by reduced levels of respirasome, the main RCS. The effects of ANT1 KD to induce RCS disassembly was not associated with acetylation of the exchanger. In conclusion, our study demonstrates that ANT is involved in RCS assembly. Full article
(This article belongs to the Special Issue Mitochondria in Health and Diseases) Printed Edition available
Show Figures

Figure 1

Open AccessArticle
Perilipin 5 Protects against Cellular Oxidative Stress by Enhancing Mitochondrial Function in HepG2 Cells
Cells 2019, 8(10), 1241; https://doi.org/10.3390/cells8101241 - 11 Oct 2019
Cited by 8 | Viewed by 1265
Abstract
: Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide. Reactive oxygen species (ROS), as potent oxidants in cells, have been shown to promote the development of NAFLD. Previous studies reported that for ROS-induced cellular oxidative stress, promoting [...] Read more.
: Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide. Reactive oxygen species (ROS), as potent oxidants in cells, have been shown to promote the development of NAFLD. Previous studies reported that for ROS-induced cellular oxidative stress, promoting lipid droplet (LD) accumulation is associated with the cellular antioxidation process. However, the regulatory role of LDs in relieving cellular oxidative stress is poorly understood. Here, we showed that Perilipin 5 (PLIN5), a key LD protein related to mitochondria–LD contact, reduced ROS levels and improved mitochondrial function in HepG2 cells. Both mRNA and protein levels of PLIN5 were significantly increased in cells with hydrogen peroxide or lipopolysaccharide (LPS) treatment (p < 0.05). Additionally, the overexpression of PLIN5 promoted LD formation and mitochondria–LD contact, reduced cellular ROS levels and up-regulated mitochondrial function-related genes such as COX and CS. Knockdown PLIN5, meanwhile, showed opposite effects. Furthermore, we identified that cellular oxidative stress up-regulated PLIN5 expression via the JNK-p38-ATF pathway. This study shows that the up-regulation of PLIN5 is a kind of survival strategy for cells in response to stress. PLIN5 can be a potential therapeutic target in NAFLD. Full article
(This article belongs to the Special Issue Mitochondria in Health and Diseases) Printed Edition available
Show Figures

Figure 1

Open AccessArticle
Mutations in NDUFS1 Cause Metabolic Reprogramming and Disruption of the Electron Transfer
Cells 2019, 8(10), 1149; https://doi.org/10.3390/cells8101149 - 25 Sep 2019
Cited by 2 | Viewed by 1123
Abstract
Complex I (CI) is the first enzyme of the mitochondrial respiratory chain and couples the electron transfer with proton pumping. Mutations in genes encoding CI subunits can frequently cause inborn metabolic errors. We applied proteome and metabolome profiling of patient-derived cells harboring pathogenic [...] Read more.
Complex I (CI) is the first enzyme of the mitochondrial respiratory chain and couples the electron transfer with proton pumping. Mutations in genes encoding CI subunits can frequently cause inborn metabolic errors. We applied proteome and metabolome profiling of patient-derived cells harboring pathogenic mutations in two distinct CI genes to elucidate underlying pathomechanisms on the molecular level. Our results indicated that the electron transfer within CI was interrupted in both patients by different mechanisms. We showed that the biallelic mutations in NDUFS1 led to a decreased stability of the entire N-module of CI and disrupted the electron transfer between two iron–sulfur clusters. Strikingly interesting and in contrast to the proteome, metabolome profiling illustrated that the pattern of dysregulated metabolites was almost identical in both patients, such as the inhibitory feedback on the TCA cycle and altered glutathione levels, indicative for reactive oxygen species (ROS) stress. Our findings deciphered pathological mechanisms of CI deficiency to better understand inborn metabolic errors. Full article
(This article belongs to the Special Issue Mitochondria in Health and Diseases) Printed Edition available
Show Figures

Figure 1

Open AccessArticle
Serine Protease HtrA2/Omi Deficiency Impairs Mitochondrial Homeostasis and Promotes Hepatic Fibrogenesis via Activation of Hepatic Stellate Cells
Cells 2019, 8(10), 1119; https://doi.org/10.3390/cells8101119 - 20 Sep 2019
Cited by 3 | Viewed by 1033
Abstract
The loss of mitochondrial function impairs intracellular energy production and potentially results in chronic liver disease. Increasing evidence suggests that mitochondrial dysfunction in hepatocytes contributes to the activation of hepatic stellate cells (HSCs), thereby resulting in hepatic fibrogenesis. High-temperature requirement protein A2 (HtrA2/Omi), [...] Read more.
The loss of mitochondrial function impairs intracellular energy production and potentially results in chronic liver disease. Increasing evidence suggests that mitochondrial dysfunction in hepatocytes contributes to the activation of hepatic stellate cells (HSCs), thereby resulting in hepatic fibrogenesis. High-temperature requirement protein A2 (HtrA2/Omi), a mitochondrial serine protease with various functions, is responsible for quality control in mitochondrial homeostasis. However, little information is available regarding its role in mitochondrial damage during the development of liver fibrosis. This study examined whether HtrA2/Omi regulates mitochondrial homeostasis in hepatocyte during the development of hepatic fibrogenesis. In this study, we demonstrated that HtrA2/Omi expression considerably decreased in liver tissues from the CCl4-induced liver fibrotic mice model and from patients with liver cirrhosis. Knockdown of HtrA2/Omi in hepatocytes induced the accumulation of damaged mitochondria and provoked mitochondrial reactive oxygen species (mtROS) stress. We further show that the damaged mtDNA isolated from HtrA2/Omi-deficient hepatocytes as a form of damage-associated molecular patterns can induce HSCs activation. Moreover, we found that motor neuron degeneration 2-mutant mice harboring the missense mutation Ser276Cys in the protease domain of HtrA2/Omi displayed altered mitochondrial morphology and function, which increased oxidative stress and promoted liver fibrosis. Conversely, the overexpression of HtrA2/Omi via hydrodynamics-based gene transfer led to the antifibrotic effects in CCl4-induced liver fibrosis mice model through decreasing collagen accumulation and enhancing anti-oxidative activity by modulating mitochondrial homeostasis in the liver. These results suggest that suppressing HtrA2/Omi expression promotes hepatic fibrogenesis via modulating mtROS generation, and these novel mechanistic insights involving the regulation of mitochondrial homeostasis by HtrA2/Omi may be of importance for developing new therapeutic strategies for hepatic fibrosis. Full article
(This article belongs to the Special Issue Mitochondria in Health and Diseases) Printed Edition available
Show Figures

Figure 1

Open AccessFeature PaperArticle
Cyclosporin A Increases Mitochondrial Buffering of Calcium: An Additional Mechanism in Delaying Mitochondrial Permeability Transition Pore Opening
Cells 2019, 8(9), 1052; https://doi.org/10.3390/cells8091052 - 07 Sep 2019
Cited by 7 | Viewed by 1535
Abstract
Regulation of mitochondrial free Ca2+ is critically important for cellular homeostasis. An increase in mitochondrial matrix free Ca2+ concentration ([Ca2+]m) predisposes mitochondria to opening of the permeability transition pore (mPTP). Opening of the pore can be delayed [...] Read more.
Regulation of mitochondrial free Ca2+ is critically important for cellular homeostasis. An increase in mitochondrial matrix free Ca2+ concentration ([Ca2+]m) predisposes mitochondria to opening of the permeability transition pore (mPTP). Opening of the pore can be delayed by cyclosporin A (CsA), possibly by inhibiting cyclophilin D (Cyp D), a key regulator of mPTP. Here, we report on a novel mechanism by which CsA delays mPTP opening by enhanced sequestration of matrix free Ca2+. Cardiac-isolated mitochondria were challenged with repetitive CaCl2 boluses under Na+-free buffer conditions with and without CsA. CsA significantly delayed mPTP opening primarily by promoting matrix Ca2+ sequestration, leading to sustained basal [Ca2+]m levels for an extended period. The preservation of basal [Ca2+]m during the CaCl2 pulse challenge was associated with normalized NADH, matrix pH (pHm), and mitochondrial membrane potential (ΔΨm). Notably, we found that in PO43− (Pi)-free buffer condition, the CsA-mediated buffering of [Ca2+]m was abrogated, and mitochondrial bioenergetics variables were concurrently compromised. In the presence of CsA, addition of Pi just before pore opening in the Pi-depleted condition reinstated the Ca2+ buffering system and rescued mitochondria from mPTP opening. This study shows that CsA promotes Pi-dependent mitochondrial Ca2+ sequestration to delay mPTP opening and, concomitantly, maintains mitochondrial function. Full article
(This article belongs to the Special Issue Mitochondria in Health and Diseases) Printed Edition available
Show Figures

Figure 1

Open AccessArticle
Pravastatin and Gemfibrozil Modulate Differently Hepatic and Colonic Mitochondrial Respiration in Tissue Homogenates from Healthy Rats
Cells 2019, 8(9), 983; https://doi.org/10.3390/cells8090983 - 27 Aug 2019
Cited by 4 | Viewed by 1036
Abstract
Statins and fibrates are widely used for the management of hypertriglyceridemia but they also have limitations, mostly due to pharmacokinetic interactions or side effects. It is conceivable that some adverse events like liver dysfunction or gastrointestinal discomfort are caused by mitochondrial dysfunction. Data [...] Read more.
Statins and fibrates are widely used for the management of hypertriglyceridemia but they also have limitations, mostly due to pharmacokinetic interactions or side effects. It is conceivable that some adverse events like liver dysfunction or gastrointestinal discomfort are caused by mitochondrial dysfunction. Data about the effects of statins and fibrates on mitochondrial function in different organs are inconsistent and partially contradictory. The aim of this study was to investigate the effect of pravastatin (statin) and gemfibrozil (fibrate) on hepatic and colonic mitochondrial respiration in tissue homogenates. Mitochondrial oxygen consumption was determined in colon and liver homogenates from 48 healthy rats after incubation with pravastatin or gemfibrozil (100, 300, 1000 μM). State 2 (substrate dependent respiration) and state 3 (adenosine diphosphate: ADP-dependent respiration) were assessed. RCI (respiratory control index)—an indicator for coupling between electron transport chain system (ETS) and oxidative phosphorylation (OXPHOS) and ADP/O ratio—a parameter for the efficacy of OXPHOS, was calculated. Data were presented as a percentage of control (Kruskal–Wallis + Dunn’s correction). In the liver both drugs reduced state 3 and RCI, gemfibrozil-reduced ADP/O (complex I). In the colon both drugs reduced state 3 but enhanced ADP/O. Pravastatin at high concentration (1000 µM) decreased RCI (complex II). Pravastatin and gemfibrozil decrease hepatic but increase colonic mitochondrial respiration in tissue homogenates from healthy rats. Full article
(This article belongs to the Special Issue Mitochondria in Health and Diseases) Printed Edition available
Show Figures

Figure 1

Open AccessArticle
BKCa (Slo) Channel Regulates Mitochondrial Function and Lifespan in Drosophila melanogaster
Cells 2019, 8(9), 945; https://doi.org/10.3390/cells8090945 - 21 Aug 2019
Cited by 7 | Viewed by 1516
Abstract
BKCa channels, originally discovered in Drosophila melanogaster as slowpoke (slo), are recognized for their roles in cellular and organ physiology. Pharmacological approaches implicated BKCa channels in cellular and organ protection possibly for their ability to modulate mitochondrial function. However, [...] Read more.
BKCa channels, originally discovered in Drosophila melanogaster as slowpoke (slo), are recognized for their roles in cellular and organ physiology. Pharmacological approaches implicated BKCa channels in cellular and organ protection possibly for their ability to modulate mitochondrial function. However, the direct role of BKCa channels in regulating mitochondrial structure and function is not deciphered. Here, we demonstrate that BKCa channels are present in fly mitochondria, and slo mutants show structural and functional defects in mitochondria. slo mutants display an increase in reactive oxygen species and the modulation of ROS affected their survival. We also found that the absence of BKCa channels reduced the lifespan of Drosophila, and overexpression of human BKCa channels in flies extends life span in males. Our study establishes the presence of BKCa channels in mitochondria of Drosophila and ascertains its novel physiological role in regulating mitochondrial structural and functional integrity, and lifespan. Full article
(This article belongs to the Special Issue Mitochondria in Health and Diseases) Printed Edition available
Show Figures

Figure 1

Open AccessArticle
Absence of Uncoupling Protein-3 at Thermoneutrality Impacts Lipid Handling and Energy Homeostasis in Mice
Cells 2019, 8(8), 916; https://doi.org/10.3390/cells8080916 - 17 Aug 2019
Cited by 4 | Viewed by 1294
Abstract
The role of uncoupling protein-3 (UCP3) in energy and lipid metabolism was investigated. Male wild-type (WT) and UCP3-null (KO) mice that were housed at thermoneutrality (30 °C) were used as the animal model. In KO mice, the ability of skeletal muscle mitochondria to [...] Read more.
The role of uncoupling protein-3 (UCP3) in energy and lipid metabolism was investigated. Male wild-type (WT) and UCP3-null (KO) mice that were housed at thermoneutrality (30 °C) were used as the animal model. In KO mice, the ability of skeletal muscle mitochondria to oxidize fatty acids (but not pyruvate or succinate) was reduced. At whole animal level, adult KO mice presented blunted resting metabolic rates, energy expenditure, food intake, and the use of lipids as metabolic substrates. When WT and KO mice were fed with a standard/low-fat diet for 80 days, since weaning, they showed similar weight gain and body composition. Interestingly, KO mice showed lower fat accumulation in visceral adipose tissue and higher ectopic fat accumulation in liver and skeletal muscle. When fed with a high-fat diet for 80 days, since weaning, KO mice showed enhanced energy efficiency and an increased lipid gain (thus leading to a change in body composition between the two genotypes). We conclude that UCP3 plays a role in energy and lipid homeostasis and in preserving lean tissues by lipotoxicity, in mice that were housed at thermoneutrality. Full article
(This article belongs to the Special Issue Mitochondria in Health and Diseases) Printed Edition available
Show Figures

Figure 1

Open AccessArticle
CDDO-Me Selectively Attenuates CA1 Neuronal Death Induced by Status Epilepticus via Facilitating Mitochondrial Fission Independent of LONP1
Cells 2019, 8(8), 833; https://doi.org/10.3390/cells8080833 - 05 Aug 2019
Cited by 9 | Viewed by 1331
Abstract
2-Cyano-3,12-dioxo-oleana-1,9(11)-dien-28-oic acid methyl ester (CDDO-Me) is a triterpenoid analogue of oleanolic acid that exhibits promising anti-cancer, anti-inflammatory, antioxidant and neuroprotective activities. In addition, CDDO-Me affects cellular differentiation and cell cycle arrest, and irreversibly inhibits Lon protease-1 (LONP1). In the present study, we evaluate [...] Read more.
2-Cyano-3,12-dioxo-oleana-1,9(11)-dien-28-oic acid methyl ester (CDDO-Me) is a triterpenoid analogue of oleanolic acid that exhibits promising anti-cancer, anti-inflammatory, antioxidant and neuroprotective activities. In addition, CDDO-Me affects cellular differentiation and cell cycle arrest, and irreversibly inhibits Lon protease-1 (LONP1). In the present study, we evaluate the effects of CDDO-Me on mitochondrial dynamics and its downstream effectors in order to understand the underlying mechanism of the neuronal death following status epilepticus (SE, a prolonged seizure activity). CDDO-Me increased dynamin-related proteins 1 (DRP1)-serine 616 phosphorylation via activating extracellular-signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK), but not protein kinase A (PKA) or protein phosphatases (PPs). In addition, CDDO-Me facilitated DRP1-mediated mitochondrial fissions, which selectively attenuated SE-induced CA1 neuronal death. Unlike CDDO-Me, LONP1 knockdown led to SE-induced massive degeneration of dentate granule cells, CA1 neurons and hilus interneurons without altering the expression and phosphorylation of DRP1, ERK1/2, JNK and PP2B. LONP1 knockdown could not inhibit SE-induced mitochondrial elongation in CA1 neurons. Co-treatment of CDDO-Me with LONP1 siRNA ameliorated only CA1 neuronal death, concomitant with abrogation of mitochondrial elongation induced by SE. Thus, our findings suggest that CDDO-Me may selectively attenuate SE-induced CA1 neuronal death by rescuing the abnormal mitochondrial machinery, independent of LONP1 activity. Full article
(This article belongs to the Special Issue Mitochondria in Health and Diseases) Printed Edition available
Show Figures

Figure 1

Open AccessArticle
Low VDAC1 Expression Is Associated with an Aggressive Phenotype and Reduced Overall Patient Survival in Cholangiocellular Carcinoma
Cells 2019, 8(6), 539; https://doi.org/10.3390/cells8060539 - 04 Jun 2019
Cited by 2 | Viewed by 1157
Abstract
Cancer cells frequently exhibit dysfunctional oxidative phosphorylation (OXPHOS) and a concomitant increase in glycolytic flux. We investigated the expression of OXPHOS complex subunits and mitochondrial mass in 34 human cholangiocellular carcinomas (CCCs) and adjacent normal tissue by using tissue microarrays. In the tumor [...] Read more.
Cancer cells frequently exhibit dysfunctional oxidative phosphorylation (OXPHOS) and a concomitant increase in glycolytic flux. We investigated the expression of OXPHOS complex subunits and mitochondrial mass in 34 human cholangiocellular carcinomas (CCCs) and adjacent normal tissue by using tissue microarrays. In the tumor periphery, all OXPHOS complexes were reduced except complex I. In addition, significantly lower levels of complex IV were found at the tumor center (p < 0.0001). Mitochondrial mass, as indicated by VDAC1 expression, was significantly increased in CCCs compared to corresponding normal tissue (p < 0.0001). VDAC1 levels were inversely correlated with UICC (Union Internationale Contre le Cancer) cancer stage classification (p = 0.0065). Furthermore, significantly lower VDAC1 was present in patients with lymph node involvement (p = 0.02). Consistent with this, patients whose carcinomas expressed VDAC1 at low to moderate levels had significantly reduced survival compared to high expressors (p < 0.05). Therefore, low mitochondrial mass is associated with more aggressive CCC. These metabolic features are indicative of a Warburg phenotype in CCCs. This metabolic signature has potential therapeutic implications because tumors with low mitochondrial function may be targeted by metabolic therapies such as a high-fat, low-carbohydrate ketogenic diet. Full article
(This article belongs to the Special Issue Mitochondria in Health and Diseases) Printed Edition available
Show Figures

Graphical abstract

Open AccessArticle
The Effects of Sodium Dichloroacetate on Mitochondrial Dysfunction and Neuronal Death Following Hypoglycemia-Induced Injury
Cells 2019, 8(5), 405; https://doi.org/10.3390/cells8050405 - 01 May 2019
Cited by 6 | Viewed by 1427
Abstract
Our previous studies demonstrated that some degree of neuronal death is caused by hypoglycemia, but a subsequent and more severe wave of neuronal cell death occurs due to glucose reperfusion, which results from the rapid restoration of low blood glucose levels. Mitochondrial dysfunction [...] Read more.
Our previous studies demonstrated that some degree of neuronal death is caused by hypoglycemia, but a subsequent and more severe wave of neuronal cell death occurs due to glucose reperfusion, which results from the rapid restoration of low blood glucose levels. Mitochondrial dysfunction caused by hypoglycemia leads to increased levels of pyruvate dehydrogenase kinase (PDK) and suppresses the formation of ATP by inhibiting pyruvate dehydrogenase (PDH) activation, which can convert pyruvate into acetyl-coenzyme A (acetyl-CoA). Sodium dichloroacetate (DCA) is a PDK inhibitor and activates PDH, the gatekeeper of glucose oxidation. However, no studies about the effect of DCA on hypoglycemia have been published. In the present study, we hypothesized that DCA treatment could reduce neuronal death through improvement of glycolysis and prevention of reactive oxygen species production after hypoglycemia. To test this, we used an animal model of insulin-induced hypoglycemia and injected DCA (100 mg/kg, i.v., two days) following hypoglycemic insult. Histological evaluation was performed one week after hypoglycemia. DCA treatment reduced hypoglycemia-induced oxidative stress, microglial activation, blood–brain barrier disruption, and neuronal death compared to the vehicle-treated hypoglycemia group. Therefore, our findings suggest that DCA may have the therapeutic potential to reduce hippocampal neuronal death after hypoglycemia. Full article
(This article belongs to the Special Issue Mitochondria in Health and Diseases) Printed Edition available
Show Figures

Figure 1

Review

Jump to: Editorial, Research

Open AccessReview
Telomeres and Telomerase in Heart Ontogenesis, Aging and Regeneration
Cells 2020, 9(2), 503; https://doi.org/10.3390/cells9020503 - 22 Feb 2020
Cited by 2 | Viewed by 1047
Abstract
The main purpose of the review article is to assess the contributions of telomere length and telomerase activity to the cardiac function at different stages of development and clarify their role in cardiac disorders. It has been shown that the telomerase complex and [...] Read more.
The main purpose of the review article is to assess the contributions of telomere length and telomerase activity to the cardiac function at different stages of development and clarify their role in cardiac disorders. It has been shown that the telomerase complex and telomeres are of great importance in many periods of ontogenesis due to the regulation of the proliferative capacity of heart cells. The review article also discusses the problems of heart regeneration and the identification of possible causes of dysfunction of telomeres and telomerase. Full article
(This article belongs to the Special Issue Mitochondria in Health and Diseases) Printed Edition available
Show Figures

Figure 1

Open AccessFeature PaperReview
Crosstalk between Mitochondria and Cytoskeleton in Cardiac Cells
Cells 2020, 9(1), 222; https://doi.org/10.3390/cells9010222 - 16 Jan 2020
Cited by 9 | Viewed by 1765
Abstract
Elucidation of the mitochondrial regulatory mechanisms for the understanding of muscle bioenergetics and the role of mitochondria is a fundamental problem in cellular physiology and pathophysiology. The cytoskeleton (microtubules, intermediate filaments, microfilaments) plays a central role in the maintenance of mitochondrial shape, location, [...] Read more.
Elucidation of the mitochondrial regulatory mechanisms for the understanding of muscle bioenergetics and the role of mitochondria is a fundamental problem in cellular physiology and pathophysiology. The cytoskeleton (microtubules, intermediate filaments, microfilaments) plays a central role in the maintenance of mitochondrial shape, location, and motility. In addition, numerous interactions between cytoskeletal proteins and mitochondria can actively participate in the regulation of mitochondrial respiration and oxidative phosphorylation. In cardiac and skeletal muscles, mitochondrial positions are tightly fixed, providing their regular arrangement and numerous interactions with other cellular structures such as sarcoplasmic reticulum and cytoskeleton. This can involve association of cytoskeletal proteins with voltage-dependent anion channel (VDAC), thereby, governing the permeability of the outer mitochondrial membrane (OMM) to metabolites, and regulating cell energy metabolism. Cardiomyocytes and myocardial fibers demonstrate regular arrangement of tubulin beta-II isoform entirely co-localized with mitochondria, in contrast to other isoforms of tubulin. This observation suggests the participation of tubulin beta-II in the regulation of OMM permeability through interaction with VDAC. The OMM permeability is also regulated by the specific isoform of cytolinker protein plectin. This review summarizes and discusses previous studies on the role of cytoskeletal proteins in the regulation of energy metabolism and mitochondrial function, adenosine triphosphate (ATP) production, and energy transfer. Full article
(This article belongs to the Special Issue Mitochondria in Health and Diseases) Printed Edition available
Show Figures

Figure 1

Open AccessReview
Mitochondrial Gene Expression and Beyond—Novel Aspects of Cellular Physiology
Cells 2020, 9(1), 17; https://doi.org/10.3390/cells9010017 - 19 Dec 2019
Cited by 7 | Viewed by 1515
Abstract
Mitochondria are peculiar organelles whose proper function depends on the crosstalk between two genomes, mitochondrial and nuclear. The human mitochondrial genome (mtDNA) encodes only 13 proteins; nevertheless, its proper expression is essential for cellular homeostasis, as mtDNA-encoded proteins are constituents of mitochondrial respiratory [...] Read more.
Mitochondria are peculiar organelles whose proper function depends on the crosstalk between two genomes, mitochondrial and nuclear. The human mitochondrial genome (mtDNA) encodes only 13 proteins; nevertheless, its proper expression is essential for cellular homeostasis, as mtDNA-encoded proteins are constituents of mitochondrial respiratory complexes. In addition, mtDNA expression results in the production of RNA molecules, which influence cell physiology once released from the mitochondria into the cytoplasm. As a result, dysfunctions of mtDNA expression may lead to pathologies in humans. Here, we review the mechanisms of mitochondrial gene expression with a focus on recent findings in the field. We summarize the complex turnover of mitochondrial transcripts and present an increasing body of evidence indicating new functions of mitochondrial transcripts. We discuss mitochondrial gene regulation in different cellular contexts, focusing on stress conditions. Finally, we highlight the importance of emerging aspects of mitochondrial gene regulation in human health and disease. Full article
(This article belongs to the Special Issue Mitochondria in Health and Diseases) Printed Edition available
Show Figures

Figure 1

Open AccessReview
Myocardial Adaptation in Pseudohypoxia: Signaling and Regulation of mPTP via Mitochondrial Connexin 43 and Cardiolipin
Cells 2019, 8(11), 1449; https://doi.org/10.3390/cells8111449 - 17 Nov 2019
Cited by 5 | Viewed by 1107
Abstract
Therapies intended to mitigate cardiovascular complications cannot be applied in practice without detailed knowledge of molecular mechanisms. Mitochondria, as the end-effector of cardioprotection, represent one of the possible therapeutic approaches. The present review provides an overview of factors affecting the regulation processes of [...] Read more.
Therapies intended to mitigate cardiovascular complications cannot be applied in practice without detailed knowledge of molecular mechanisms. Mitochondria, as the end-effector of cardioprotection, represent one of the possible therapeutic approaches. The present review provides an overview of factors affecting the regulation processes of mitochondria at the level of mitochondrial permeability transition pores (mPTP) resulting in comprehensive myocardial protection. The regulation of mPTP seems to be an important part of the mechanisms for maintaining the energy equilibrium of the heart under pathological conditions. Mitochondrial connexin 43 is involved in the regulation process by inhibition of mPTP opening. These individual cardioprotective mechanisms can be interconnected in the process of mitochondrial oxidative phosphorylation resulting in the maintenance of adenosine triphosphate (ATP) production. In this context, the degree of mitochondrial membrane fluidity appears to be a key factor in the preservation of ATP synthase rotation required for ATP formation. Moreover, changes in the composition of the cardiolipin’s structure in the mitochondrial membrane can significantly affect the energy system under unfavorable conditions. This review aims to elucidate functional and structural changes of cardiac mitochondria subjected to preconditioning, with an emphasis on signaling pathways leading to mitochondrial energy maintenance during partial oxygen deprivation. Full article
(This article belongs to the Special Issue Mitochondria in Health and Diseases) Printed Edition available
Show Figures

Figure 1

Open AccessReview
Mitochondrial Involvement in the Adaptive Response to Chronic Exposure to Environmental Pollutants and High-Fat Feeding in a Rat Liver and Testis
Cells 2019, 8(8), 834; https://doi.org/10.3390/cells8080834 - 05 Aug 2019
Cited by 4 | Viewed by 1235
Abstract
In our modern society, exposure to stressful environmental stimuli, such as pollutants and/or chronic high-fat feeding, continuously induce tissular/organ metabolic adaptation to promote cellular survival. In extreme conditions, cellular death and tissular/organ damage occur. Mitochondria, as a cellular energy source, seem to play [...] Read more.
In our modern society, exposure to stressful environmental stimuli, such as pollutants and/or chronic high-fat feeding, continuously induce tissular/organ metabolic adaptation to promote cellular survival. In extreme conditions, cellular death and tissular/organ damage occur. Mitochondria, as a cellular energy source, seem to play an important role in facing cellular stress induced by these environmental stimuli. On the other hand, mitochondrial dysfunction and oxidative stress play a key role in environmental stress-induced metabolic diseases. However, little is known about the combined effect of simultaneous exposure to chronic high-fat feeding and environmental pollutants on metabolic alterations at a tissular and cellular level, including mitochondrial dysfunction and oxidative stress induction. Our research group recently addressed this topic by analysing the effect of chronic exposure to a non-toxic dose of the environmental pollutant dichlorodiphenyldichloroethylene (DDE) associated with high-fat feeding in male Wistar rats. In this review, we mainly summarize our recent findings on mitochondrial adaptive response and oxidative stress induction in the liver, the main tissue involved in fat metabolism and pollutant detoxification, and in male gonads, the main targets of endocrine disruption induced by both high-fat feeding and environmental pollutants. Full article
(This article belongs to the Special Issue Mitochondria in Health and Diseases) Printed Edition available
Show Figures

Figure 1

Back to TopTop