Mitochondria-targeted drug delivery

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: closed (20 December 2020) | Viewed by 48008

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Department of Oncology, University of Turin, Turin, Italy
Interests: thoracic neoplasms, immunoresistance, chemoresistance, new therapeutic approaches against tumors
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Dear Colleagues,

Mitochondria, organelles surrounded by a double membrane and with their own small genome, are the cells’ energy centers. Besides the production of ATP through cellular respiration, mitochondria play a pivotal role in other aspects of the life and death of a cell: heat production, programmed cell death, regulation of metabolic activity, immunity, and calcium homeostasis. A number of diseases are associated with mitochondrial dysfunction, including cardiovascular, neurological, inflammatory, and metabolic disorders and cancer. Mitochondria therefore represent an important therapy target, and it is not surprising that a number of different treatment strategies have emerged. Approaches targeting mitochondria can be split into two opposite categories: drugs that restore mitochondrial function and drugs that trigger mitochondria-mediated cell death. Targeted drug delivery to obtain selective accumulation of drug molecules in mitochondria is complex and involves methods such as direct drug modification or encapsulation into nanocarriers.

This Special Issue’s goal is to present the current state of the art in the field. We invite reviews or original articles on mitochondria as a promising target for treating a wide range of human diseases and pathological conditions, as well as articles on recent approaches for mitochondria-targeted drug delivery.

Dr. Joanna Kopecka
Guest Editor

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Keywords

  • Mitochondria
  • Mitochondrial metabolism
  • Mitochondrial disease
  • Mitochondria-targeted drugs
  • Targeting strategies
  • Drug delivery
  • Nanocarriers

Published Papers (13 papers)

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Editorial

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3 pages, 161 KiB  
Editorial
Mitochondria-Targeted Drug Delivery
by Joanna Kopecka
Pharmaceutics 2022, 14(1), 178; https://doi.org/10.3390/pharmaceutics14010178 - 13 Jan 2022
Cited by 2 | Viewed by 1734
Abstract
Mitochondria, organelles surrounded by a double membrane and with their own small genome, are the cells’ energy centres [...] Full article
(This article belongs to the Special Issue Mitochondria-targeted drug delivery)

Research

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15 pages, 17711 KiB  
Article
Plumbagin Elicits Cell-Specific Cytotoxic Effects and Metabolic Responses in Melanoma Cells
by Haoran Zhang, Aijun Zhang, Anisha A. Gupte and Dale J. Hamilton
Pharmaceutics 2021, 13(5), 706; https://doi.org/10.3390/pharmaceutics13050706 - 12 May 2021
Cited by 5 | Viewed by 2341
Abstract
Melanoma is one of the most malignant skin cancers that require comprehensive therapies, including chemotherapy. A plant-derived drug, plumbagin (PLB), exhibits an anticancer property in several cancers. We compared the cytotoxic and metabolic roles of PLB in A375 and SK-MEL-28 cells, each with [...] Read more.
Melanoma is one of the most malignant skin cancers that require comprehensive therapies, including chemotherapy. A plant-derived drug, plumbagin (PLB), exhibits an anticancer property in several cancers. We compared the cytotoxic and metabolic roles of PLB in A375 and SK-MEL-28 cells, each with different aggressiveness. In our results, they were observed to have distinctive mitochondrial respiratory functions. The primary reactive oxygen species (ROS) source of A375 can be robustly attenuated by cell membrane permeabilization. A375 cell viability and proliferation, migration, and apoptosis induction are more sensitive to PLB treatment. PLB induced metabolic alternations in SK-MEL-28 cells, which included increasing mitochondrial oxidative phosphorylation (OXPHOS), mitochondrial ATP production, and mitochondrial mass. Decreasing mitochondrial OXPHOS and total ATP production with elevated mitochondrial membrane potential (MMP) were observed in PLB-induced A375 cells. PLB also induced ROS production and increased proton leak and non-mitochondria respiration in both cells. This study reveals the relationship between metabolism and cytotoxic effects of PLB in melanoma. PLB displays stronger cytotoxic effects on A375 cells, which exhibit lower respiratory function than SK-MEL-28 cells with higher respiratory function, and triggers cell-specific metabolic changes in accordance with its cytotoxic effects. These findings indicate that PLB might serve as a promising anticancer drug, targeting metabolism. Full article
(This article belongs to the Special Issue Mitochondria-targeted drug delivery)
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18 pages, 8481 KiB  
Article
Chimeric Drug Design with a Noncharged Carrier for Mitochondrial Delivery
by Consuelo Ripoll, Pilar Herrero-Foncubierta, Virginia Puente-Muñoz, M. Carmen Gonzalez-Garcia, Delia Miguel, Sandra Resa, Jose M. Paredes, Maria J. Ruedas-Rama, Emilio Garcia-Fernandez, Mar Roldan, Susana Rocha, Herlinde De Keersmaecker, Johan Hofkens, Miguel Martin, Juan M. Cuerva and Angel Orte
Pharmaceutics 2021, 13(2), 254; https://doi.org/10.3390/pharmaceutics13020254 - 12 Feb 2021
Cited by 5 | Viewed by 2909
Abstract
Recently, it was proposed that the thiophene ring is capable of promoting mitochondrial accumulation when linked to fluorescent markers. As a noncharged group, thiophene presents several advantages from a synthetic point of view, making it easier to incorporate such a side moiety into [...] Read more.
Recently, it was proposed that the thiophene ring is capable of promoting mitochondrial accumulation when linked to fluorescent markers. As a noncharged group, thiophene presents several advantages from a synthetic point of view, making it easier to incorporate such a side moiety into different molecules. Herein, we confirm the general applicability of the thiophene group as a mitochondrial carrier for drugs and fluorescent markers based on a new concept of nonprotonable, noncharged transporter. We implemented this concept in a medicinal chemistry application by developing an antitumor, metabolic chimeric drug based on the pyruvate dehydrogenase kinase (PDHK) inhibitor dichloroacetate (DCA). The promising features of the thiophene moiety as a noncharged carrier for targeting mitochondria may represent a starting point for the design of new metabolism-targeting drugs. Full article
(This article belongs to the Special Issue Mitochondria-targeted drug delivery)
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19 pages, 3856 KiB  
Article
Effect of Diphenyleneiodonium Chloride on Intracellular Reactive Oxygen Species Metabolism with Emphasis on NADPH Oxidase and Mitochondria in Two Therapeutically Relevant Human Cell Types
by Sergejs Zavadskis, Adelheid Weidinger, Dominik Hanetseder, Asmita Banerjee, Cornelia Schneider, Susanne Wolbank, Darja Marolt Presen and Andrey V. Kozlov
Pharmaceutics 2021, 13(1), 10; https://doi.org/10.3390/pharmaceutics13010010 - 23 Dec 2020
Cited by 7 | Viewed by 3506
Abstract
Reactive oxygen species (ROS) have recently been recognized as important signal transducers, particularly regulating proliferation and differentiation of cells. Diphenyleneiodonium (DPI) is known as an inhibitor of the nicotinamide adenine dinucleotide phosphate oxidase (NOX) and is also affecting mitochondrial function. The aim of [...] Read more.
Reactive oxygen species (ROS) have recently been recognized as important signal transducers, particularly regulating proliferation and differentiation of cells. Diphenyleneiodonium (DPI) is known as an inhibitor of the nicotinamide adenine dinucleotide phosphate oxidase (NOX) and is also affecting mitochondrial function. The aim of this study was to investigate the effect of DPI on ROS metabolism and mitochondrial function in human amniotic membrane mesenchymal stromal cells (hAMSCs), human bone marrow mesenchymal stromal cells (hBMSCs), hBMSCs induced into osteoblast-like cells, and osteosarcoma cell line MG-63. Our data suggested a combination of a membrane potential sensitive fluorescent dye, tetramethylrhodamine methyl ester (TMRM), and a ROS-sensitive dye, CM-H2DCFDA, combined with a pretreatment with mitochondria-targeted ROS scavenger MitoTEMPO as a good tool to examine effects of DPI. We observed critical differences in ROS metabolism between hAMSCs, hBMSCs, osteoblast-like cells, and MG-63 cells, which were linked to energy metabolism. In cell types using predominantly glycolysis as the energy source, such as hAMSCs, DPI predominantly interacted with NOX, and it was not toxic for the cells. In hBMSCs, the ROS turnover was influenced by NOX activity rather than by the mitochondria. In cells with aerobic metabolism, such as MG 63, the mitochondria became an additional target for DPI, and these cells were prone to the toxic effects of DPI. In summary, our data suggest that undifferentiated cells rather than differentiated parenchymal cells should be considered as potential targets for DPI. Full article
(This article belongs to the Special Issue Mitochondria-targeted drug delivery)
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13 pages, 1741 KiB  
Article
Oxoglutarate Carrier Inhibition Reduced Melanoma Growth and Invasion by Reducing ATP Production
by Jae-Seon Lee, Jiwon Choi, Seon-Hyeong Lee, Joon Hee Kang, Ji Sun Ha, Hee Yeon Kim, Hyonchol Jang, Jong In Yook and Soo-Youl Kim
Pharmaceutics 2020, 12(11), 1128; https://doi.org/10.3390/pharmaceutics12111128 - 23 Nov 2020
Cited by 5 | Viewed by 2229
Abstract
Recent findings indicate that (a) mitochondria in proliferating cancer cells are functional, (b) cancer cells use more oxygen than normal cells for oxidative phosphorylation, and (c) cancer cells critically rely on cytosolic NADH transported into mitochondria via the malate-aspartate shuttle (MAS) for ATP [...] Read more.
Recent findings indicate that (a) mitochondria in proliferating cancer cells are functional, (b) cancer cells use more oxygen than normal cells for oxidative phosphorylation, and (c) cancer cells critically rely on cytosolic NADH transported into mitochondria via the malate-aspartate shuttle (MAS) for ATP production. In a spontaneous lung cancer model, tumor growth was reduced by 50% in heterozygous oxoglutarate carrier (OGC) knock-out mice compared with wild-type counterparts. To determine the mechanism through which OGC promotes tumor growth, the effects of the OGC inhibitor N-phenylmaleimide (NPM) on mitochondrial activity, oxygen consumption, and ATP production were evaluated in melanoma cell lines. NPM suppressed oxygen consumption and decreased ATP production in melanoma cells in a dose-dependent manner. NPM also reduced the proliferation of melanoma cells. To test the effects of NPM on tumor growth and metastasis in vivo, NPM was administered in a human melanoma xenograft model. NPM reduced tumor growth by approximately 50% and reduced melanoma invasion by 70% at a dose of 20 mg/kg. Therefore, blocking OGC activity may be a useful approach for cancer therapy. Full article
(This article belongs to the Special Issue Mitochondria-targeted drug delivery)
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14 pages, 1059 KiB  
Article
CancerGram: An Effective Classifier for Differentiating Anticancer from Antimicrobial Peptides
by Michał Burdukiewicz, Katarzyna Sidorczuk, Dominik Rafacz, Filip Pietluch, Mateusz Bąkała, Jadwiga Słowik and Przemysław Gagat
Pharmaceutics 2020, 12(11), 1045; https://doi.org/10.3390/pharmaceutics12111045 - 31 Oct 2020
Cited by 20 | Viewed by 4011
Abstract
Antimicrobial peptides (AMPs) constitute a diverse group of bioactive molecules that provide multicellular organisms with protection against microorganisms, and microorganisms with weaponry for competition. Some AMPs can target cancer cells; thus, they are called anticancer peptides (ACPs). Due to their small size, positive [...] Read more.
Antimicrobial peptides (AMPs) constitute a diverse group of bioactive molecules that provide multicellular organisms with protection against microorganisms, and microorganisms with weaponry for competition. Some AMPs can target cancer cells; thus, they are called anticancer peptides (ACPs). Due to their small size, positive charge, hydrophobicity and amphipathicity, AMPs and ACPs interact with negatively charged components of biological membranes. AMPs preferentially permeabilize microbial membranes, but ACPs additionally target mitochondrial and plasma membranes of cancer cells. The preference towards mitochondrial membranes is explained by their membrane potential, membrane composition resulting from α-proteobacterial origin and the fact that mitochondrial targeting signals could have evolved from AMPs. Taking into account the therapeutic potential of ACPs and millions of deaths due to cancer annually, it is of vital importance to find new cationic peptides that selectively destroy cancer cells. Therefore, to reduce the costs of experimental research, we have created a robust computational tool, CancerGram, that uses n-grams and random forests for predicting ACPs. Compared to other ACP classifiers, CancerGram is the first three-class model that effectively classifies peptides into: ACPs, AMPs and non-ACPs/non-AMPs, with AU1U amounting to 0.89 and a Kappa statistic of 0.65. CancerGram is available as a web server and R package on GitHub. Full article
(This article belongs to the Special Issue Mitochondria-targeted drug delivery)
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Review

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20 pages, 1186 KiB  
Review
Engineering Genetic Systems for Treating Mitochondrial Diseases
by Yoon-ha Jang, Sae Ryun Ahn, Ji-yeon Shim and Kwang-il Lim
Pharmaceutics 2021, 13(6), 810; https://doi.org/10.3390/pharmaceutics13060810 - 28 May 2021
Cited by 7 | Viewed by 3081
Abstract
Mitochondria are intracellular energy generators involved in various cellular processes. Therefore, mitochondrial dysfunction often leads to multiple serious diseases, including neurodegenerative and cardiovascular diseases. A better understanding of the underlying mitochondrial dysfunctions of the molecular mechanism will provide important hints on how to [...] Read more.
Mitochondria are intracellular energy generators involved in various cellular processes. Therefore, mitochondrial dysfunction often leads to multiple serious diseases, including neurodegenerative and cardiovascular diseases. A better understanding of the underlying mitochondrial dysfunctions of the molecular mechanism will provide important hints on how to mitigate the symptoms of mitochondrial diseases and eventually cure them. In this review, we first summarize the key parts of the genetic processes that control the physiology and functions of mitochondria and discuss how alterations of the processes cause mitochondrial diseases. We then list up the relevant core genetic components involved in these processes and explore the mutations of the components that link to the diseases. Lastly, we discuss recent attempts to apply multiple genetic methods to alleviate and further reverse the adverse effects of the core component mutations on the physiology and functions of mitochondria. Full article
(This article belongs to the Special Issue Mitochondria-targeted drug delivery)
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28 pages, 2560 KiB  
Review
Mitochondrial Targeting Involving Cholesterol-Rich Lipid Rafts in the Mechanism of Action of the Antitumor Ether Lipid and Alkylphospholipid Analog Edelfosine
by Faustino Mollinedo and Consuelo Gajate
Pharmaceutics 2021, 13(5), 763; https://doi.org/10.3390/pharmaceutics13050763 - 20 May 2021
Cited by 13 | Viewed by 3793
Abstract
The ether lipid edelfosine induces apoptosis selectively in tumor cells and is the prototypic molecule of a family of synthetic antitumor compounds collectively known as alkylphospholipid analogs. Cumulative evidence shows that edelfosine interacts with cholesterol-rich lipid rafts, endoplasmic reticulum (ER) and mitochondria. Edelfosine [...] Read more.
The ether lipid edelfosine induces apoptosis selectively in tumor cells and is the prototypic molecule of a family of synthetic antitumor compounds collectively known as alkylphospholipid analogs. Cumulative evidence shows that edelfosine interacts with cholesterol-rich lipid rafts, endoplasmic reticulum (ER) and mitochondria. Edelfosine induces apoptosis in a number of hematological cancer cells by recruiting death receptors and downstream apoptotic signaling into lipid rafts, whereas it promotes apoptosis in solid tumor cells through an ER stress response. Edelfosine-induced apoptosis, mediated by lipid rafts and/or ER, requires the involvement of a mitochondrial-dependent step to eventually elicit cell death, leading to the loss of mitochondrial membrane potential, cytochrome c release and the triggering of cell death. The overexpression of Bcl-2 or Bcl-xL blocks edelfosine-induced apoptosis. Edelfosine induces the redistribution of lipid rafts from the plasma membrane to the mitochondria. The pro-apoptotic action of edelfosine on cancer cells is associated with the recruitment of F1FO–ATP synthase into cholesterol-rich lipid rafts. Specific inhibition of the FO sector of the F1FO–ATP synthase, which contains the membrane-embedded c-subunit ring that constitutes the mitochondrial permeability transcription pore, hinders edelfosine-induced cell death. Taking together, the evidence shown here suggests that the ether lipid edelfosine could modulate cell death in cancer cells by direct interaction with mitochondria, and the reorganization of raft-located mitochondrial proteins that critically modulate cell death or survival. Here, we summarize and discuss the involvement of mitochondria in the antitumor action of the ether lipid edelfosine, pointing out the mitochondrial targeting of this drug as a major therapeutic approach, which can be extrapolated to other alkylphospholipid analogs. We also discuss the involvement of cholesterol transport and cholesterol-rich lipid rafts in the interactions between the organelles as well as in the role of mitochondria in the regulation of apoptosis in cancer cells and cancer therapy. Full article
(This article belongs to the Special Issue Mitochondria-targeted drug delivery)
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15 pages, 1241 KiB  
Review
Targeting Mitochondrial Oncometabolites: A New Approach to Overcome Drug Resistance in Cancer
by Martina Godel, Giacomo Ortone, Dario Pasquale Anobile, Martina Pasino, Giulio Randazzo, Chiara Riganti and Joanna Kopecka
Pharmaceutics 2021, 13(5), 762; https://doi.org/10.3390/pharmaceutics13050762 - 20 May 2021
Cited by 15 | Viewed by 3248
Abstract
Drug resistance is the main obstacle for a successful cancer therapy. There are many mechanisms by which cancers avoid drug-mediated death, including alterations in cellular metabolism and apoptotic programs. Mitochondria represent the cell’s powerhouse and the connection between carbohydrate, lipid and proteins metabolism, [...] Read more.
Drug resistance is the main obstacle for a successful cancer therapy. There are many mechanisms by which cancers avoid drug-mediated death, including alterations in cellular metabolism and apoptotic programs. Mitochondria represent the cell’s powerhouse and the connection between carbohydrate, lipid and proteins metabolism, as well as crucial controllers of apoptosis, playing an important role not only in tumor growth and progression, but also in drug response. Alterations in tricarboxylic acid cycle (TCA) caused by mutations in three TCA enzymes—isocitrate dehydrogenase, succinate dehydrogenase and fumarate hydratase—lead to the accumulation of 2-hydroxyglutarate, succinate and fumarate respectively, collectively known as oncometabolites. Oncometabolites have pleiotropic effects on cancer biology. For instance, they generate a pseudohypoxic phenotype and induce epigenetic changes, two factors that may promote cancer drug resistance leading to disease progression and poor therapy outcome. This review sums up the most recent findings about the role of TCA-derived oncometabolites in cancer aggressiveness and drug resistance, highlighting possible pharmacological strategies targeting oncometabolites production in order to improve the efficacy of cancer treatment. Full article
(This article belongs to the Special Issue Mitochondria-targeted drug delivery)
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24 pages, 965 KiB  
Review
Protective Effect of Mitochondria-Targeted Antioxidants against Inflammatory Response to Lipopolysaccharide Challenge: A Review
by Ekaterina M. Fock and Rimma G. Parnova
Pharmaceutics 2021, 13(2), 144; https://doi.org/10.3390/pharmaceutics13020144 - 22 Jan 2021
Cited by 27 | Viewed by 3190
Abstract
Lipopolysaccharide (LPS), the major component of the outer membrane of Gram-negative bacteria, is the most abundant proinflammatory agent. Considerable evidence indicates that LPS challenge inescapably causes oxidative stress and mitochondrial dysfunction, leading to cell and tissue damage. Increased mitochondrial reactive oxygen species (mtROS) [...] Read more.
Lipopolysaccharide (LPS), the major component of the outer membrane of Gram-negative bacteria, is the most abundant proinflammatory agent. Considerable evidence indicates that LPS challenge inescapably causes oxidative stress and mitochondrial dysfunction, leading to cell and tissue damage. Increased mitochondrial reactive oxygen species (mtROS) generation triggered by LPS is known to play a key role in the progression of the inflammatory response. mtROS at excessive levels impair electron transport chain functioning, reduce the mitochondrial membrane potential, and initiate lipid peroxidation and oxidative damage of mitochondrial proteins and mtDNA. Over the past 20 years, a large number of mitochondria-targeted antioxidants (mito-AOX) of different structures that can accumulate inside mitochondria and scavenge free radicals have been synthesized. Their protective role based on the prevention of oxidative stress and the restoration of mitochondrial function has been demonstrated in a variety of common diseases and pathological states. This paper reviews the current data on the beneficial application of different mito-AOX in animal endotoxemia models, in either in vivo or in vitro experiments. The results presented in our review demonstrate the promising potential of approaches based on mito-AOX in the development of new treatment strategies against Gram-negative infections and LPS per se. Full article
(This article belongs to the Special Issue Mitochondria-targeted drug delivery)
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24 pages, 2239 KiB  
Review
Mitochondria-Targeted Drug Delivery in Cardiovascular Disease: A Long Road to Nano-Cardio Medicine
by Francesca Forini, Paola Canale, Giuseppina Nicolini and Giorgio Iervasi
Pharmaceutics 2020, 12(11), 1122; https://doi.org/10.3390/pharmaceutics12111122 - 20 Nov 2020
Cited by 29 | Viewed by 4394
Abstract
Cardiovascular disease (CVD) represents a major threat for human health. The available preventive and treatment interventions are insufficient to revert the underlying pathological processes, which underscores the urgency of alternative approaches. Mitochondria dysfunction plays a key role in the etiopathogenesis of CVD and [...] Read more.
Cardiovascular disease (CVD) represents a major threat for human health. The available preventive and treatment interventions are insufficient to revert the underlying pathological processes, which underscores the urgency of alternative approaches. Mitochondria dysfunction plays a key role in the etiopathogenesis of CVD and is regarded as an intriguing target for the development of innovative therapies. Oxidative stress, mitochondrial permeability transition pore opening, and excessive fission are major noxious pathways amenable to drug therapy. Thanks to the advancements of nanotechnology research, several mitochondria-targeted drug delivery systems (DDS) have been optimized with improved pharmacokinetic and biocompatibility, and lower toxicity and antigenicity for application in the cardiovascular field. This review summarizes the recent progress and remaining obstacles in targeting mitochondria as a novel therapeutic option for CVD. The advantages of nanoparticle delivery over un-targeted strategies are also discussed. Full article
(This article belongs to the Special Issue Mitochondria-targeted drug delivery)
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63 pages, 2166 KiB  
Review
Therapeutic Approaches to Treat Mitochondrial Diseases: “One-Size-Fits-All” and “Precision Medicine” Strategies
by Emanuela Bottani, Costanza Lamperti, Alessandro Prigione, Valeria Tiranti, Nicola Persico and Dario Brunetti
Pharmaceutics 2020, 12(11), 1083; https://doi.org/10.3390/pharmaceutics12111083 - 11 Nov 2020
Cited by 45 | Viewed by 9265
Abstract
Primary mitochondrial diseases (PMD) refer to a group of severe, often inherited genetic conditions due to mutations in the mitochondrial genome or in the nuclear genes encoding for proteins involved in oxidative phosphorylation (OXPHOS). The mutations hamper the last step of aerobic metabolism, [...] Read more.
Primary mitochondrial diseases (PMD) refer to a group of severe, often inherited genetic conditions due to mutations in the mitochondrial genome or in the nuclear genes encoding for proteins involved in oxidative phosphorylation (OXPHOS). The mutations hamper the last step of aerobic metabolism, affecting the primary source of cellular ATP synthesis. Mitochondrial diseases are characterized by extremely heterogeneous symptoms, ranging from organ-specific to multisystemic dysfunction with different clinical courses. The limited information of the natural history, the limitations of currently available preclinical models, coupled with the large variability of phenotypical presentations of PMD patients, have strongly penalized the development of effective therapies. However, new therapeutic strategies have been emerging, often with promising preclinical and clinical results. Here we review the state of the art on experimental treatments for mitochondrial diseases, presenting “one-size-fits-all” approaches and precision medicine strategies. Finally, we propose novel perspective therapeutic plans, either based on preclinical studies or currently used for other genetic or metabolic diseases that could be transferred to PMD. Full article
(This article belongs to the Special Issue Mitochondria-targeted drug delivery)
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18 pages, 959 KiB  
Review
Stem Cells as Drug-like Biologics for Mitochondrial Repair in Stroke
by Jeffrey Farooq, You Jeong Park, Justin Cho, Madeline Saft, Nadia Sadanandan, Blaise Cozene and Cesar V. Borlongan
Pharmaceutics 2020, 12(7), 615; https://doi.org/10.3390/pharmaceutics12070615 - 1 Jul 2020
Cited by 5 | Viewed by 3132
Abstract
Stroke is a devastating condition characterized by widespread cell death after disruption of blood flow to the brain. The poor regenerative capacity of neural cells limits substantial recovery and prolongs disruptive sequelae. Current therapeutic options are limited and do not adequately address the [...] Read more.
Stroke is a devastating condition characterized by widespread cell death after disruption of blood flow to the brain. The poor regenerative capacity of neural cells limits substantial recovery and prolongs disruptive sequelae. Current therapeutic options are limited and do not adequately address the underlying mitochondrial dysfunction caused by the stroke. These same mitochondrial impairments that result from acute cerebral ischemia are also present in retinal ischemia. In both cases, sufficient mitochondrial activity is necessary for cell survival, and while astrocytes are able to transfer mitochondria to damaged tissues to rescue them, they do not have the capacity to completely repair damaged tissues. Therefore, it is essential to investigate this mitochondrial transfer pathway as a target of future therapeutic strategies. In this review, we examine the current literature pertinent to mitochondrial repair in stroke, with an emphasis on stem cells as a source of healthy mitochondria. Stem cells are a compelling cell type to study in this context, as their ability to mitigate stroke-induced damage through non-mitochondrial mechanisms is well established. Thus, we will focus on the latest preclinical research relevant to mitochondria-based mechanisms in the treatment of cerebral and retinal ischemia and consider which stem cells are ideally suited for this purpose. Full article
(This article belongs to the Special Issue Mitochondria-targeted drug delivery)
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