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Mitochondrial Function in Human Health and Disease: 2nd Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: 20 July 2025 | Viewed by 5184

Special Issue Editor

Department of Medicine, Division of Endocrinology, University of California, Irvine, CA 92697, USA
Interests: cell cycle checkpoint control; DNA damage and repair pathway; Nek1 protein kinase; polycystic kidney disease; AKT and mitochondrial function
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Mitochondria play critical metabolic roles in fatty acid oxidation, the Krebs cycle, and oxidative phosphorylation. All of these metabolic processes result in reactive oxygen species (ROS) production. ROS are toxic to cells as they cause oxidative damage to mitochondrial lipids, DNA, and proteins. Damaged mitochondria also release high levels of Ca2+ and cytochrome C, inducing apoptosis. To control the quality and quantity of mitochondria, selective autophagy, known as mitophagy, plays an important role by eliminating damaged mitochondria. Besides causing ROS damage in mitochondria, alterations in mitochondrial function through mutations in either the mitochondrial or nuclear genome have also been found to be associated with various diseases, such as cancer, aging, metabolic disorders, etc. The first known involvement of mitochondria in cancer came from Warburg’s landmark observation that tumors produce excess lactate in the presence of oxygen, now known as the “Warburg effect”, which is a form of aerobic glycolysis. The activation of cellular signaling transduction pathways, such as the PI3’K/PTEN/Akt pathway, also plays an important role in shifting metabolism from oxidative to glycolytic phosphorylation. Now, more evidence suggests that AKT kinase activity in mitochondria is crucial for cellular defense to extrinsic insults such as ischemia reperfusion. This Special Issue elucidates various aspects of mitochondrial function in cancer, kidney disease, apoptosis, and autophagy, and further discusses the therapeutic potential of targeting mitochondria.

Dr. Yumay Chen
Guest Editor

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Keywords

  • mitochondial genesis and disease
  • mitochondrial function and aging
  • mitochondrial dysfunction and cancer
  • mitochondrial function and apoptosis
  • mitophage
  • autophage
  • mitochondrial AKT
 

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Related Special Issue

Published Papers (3 papers)

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Research

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22 pages, 6338 KiB  
Article
Oxidative High Mobility Group Box-1 Accelerates Mitochondrial Transfer from Mesenchymal Stem Cells to Colorectal Cancer Cells Providing Cancer Cell Stemness
by Rika Sasaki, Yi Luo, Shingo Kishi, Ruiko Ogata, Yukiko Nishiguchi, Takamitsu Sasaki, Hitoshi Ohmori, Rina Fujiwara-Tani and Hiroki Kuniyasu
Int. J. Mol. Sci. 2025, 26(3), 1192; https://doi.org/10.3390/ijms26031192 - 30 Jan 2025
Viewed by 844
Abstract
Mitochondria are important organelles for cell metabolism and tissue survival. Their cell-to-cell transfer is important for the fate of recipient cells. Recently, bone marrow mesenchymal stem cells (BM-MSCs) have been reported to provide mitochondria to cancer cells and rescue mitochondrial dysfunction in cancer [...] Read more.
Mitochondria are important organelles for cell metabolism and tissue survival. Their cell-to-cell transfer is important for the fate of recipient cells. Recently, bone marrow mesenchymal stem cells (BM-MSCs) have been reported to provide mitochondria to cancer cells and rescue mitochondrial dysfunction in cancer cells. However, the details of the mechanism have not yet been fully elucidated. In this study, we investigated the humoral factors inducing mitochondrial transfer (MT) and the mechanisms. BM-MSCs produced MT in colorectal cancer (CRC) cells damaged by 5-fluorouracil (5-FU), but were suppressed by the anti-high mobility group box-1 (HMGB1) antibody. BM-MSCs treated with oxidized HMGB1 had increased expression of MT-associated genes, whereas reduced HMGB1 did not. Inhibition of nuclear factor–κB, a downstream factor of HMGB1 signaling, significantly decreased MT-associated gene expression. CRC cells showed increased stemness and decreased 5-FU sensitivity in correlation with MT levels. In a mouse subcutaneous tumor model of CRC, 5-FU sensitivity decreased and stemness increased by the MT from host mouse BM-MSCs. These results suggest that oxidized HMGB1 induces MTs from MSCs to CRC cells and promotes cancer cell stemness. Targeting of oxidized HMGB1 may attenuate stemness of CRCs. Full article
(This article belongs to the Special Issue Mitochondrial Function in Human Health and Disease: 2nd Edition)
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17 pages, 2909 KiB  
Article
Mass Spectrometry Analysis of Neurotransmitter Shifting during Neurogenesis and Neurodegeneration of PC12 Cells
by Yu-Ning Jao, Yu-Jen Chao, Jui-Fen Chan and Yuan-Hao Howard Hsu
Int. J. Mol. Sci. 2024, 25(19), 10399; https://doi.org/10.3390/ijms251910399 - 27 Sep 2024
Cited by 1 | Viewed by 987
Abstract
Parkinson’s disease (PD) affects movement; however, most patients with PD also develop nonmotor symptoms, such as hyposmia, sleep disorder, and depression. Dopamine levels in the brain have a critical influence on movement control, but other neurotransmitters are also involved in the progression of [...] Read more.
Parkinson’s disease (PD) affects movement; however, most patients with PD also develop nonmotor symptoms, such as hyposmia, sleep disorder, and depression. Dopamine levels in the brain have a critical influence on movement control, but other neurotransmitters are also involved in the progression of PD. This study analyzed the fluctuation of neurotransmitters in PC12 cells during neurogenesis and neurodegeneration by performing mass spectrometry. We found that the dopaminergic metabolism pathway of PC12 cells developed vigorously during the neuron differentiation process and that the neurotransmitters were metabolized into 3-methoxytyramine, which was released from the cells. The regulation of the intracellular and extracellular concentrations of adenosine indicated that adenine nucleotides were actively utilized in neural differentiation. Moreover, we exposed the differentiated PC12 cells to rotenone, which is a suitable material for modeling PD. The cells exposed to rotenone in the early stage of differentiation exhibited stimulated serotoninergic metabolism, and the contents of the serotoninergic neurotransmitters returned to their normal levels in the late stage of differentiation. Interestingly, the nondifferentiated cells can resist the toxicant rotenone and produce normal dopaminergic metabolites. However, when differentiated neuron cells were exposed to rotenone, they were seriously damaged, leading to a failure to produce dopaminergic neurotransmitters. In the low-dosage damage process, the amino acids that functioned as dopaminergic pathway precursors could not be absorbed by the cells, and dopamine and L-dopa were secreted and unable to be reuptaken to trigger the cell damage. Full article
(This article belongs to the Special Issue Mitochondrial Function in Human Health and Disease: 2nd Edition)
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Review

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33 pages, 2994 KiB  
Review
Mitochondrial Aconitase and Its Contribution to the Pathogenesis of Neurodegenerative Diseases
by Volodymyr Padalko, Filip Posnik and Malgorzata Adamczyk
Int. J. Mol. Sci. 2024, 25(18), 9950; https://doi.org/10.3390/ijms25189950 - 15 Sep 2024
Cited by 6 | Viewed by 2666
Abstract
This survey reviews modern ideas on the structure and functions of mitochondrial and cytosolic aconitase isoenzymes in eukaryotes. Cumulative experimental evidence about mitochondrial aconitases (Aco2) as one of the main targets of reactive oxygen and nitrogen species is generalized. The important role of [...] Read more.
This survey reviews modern ideas on the structure and functions of mitochondrial and cytosolic aconitase isoenzymes in eukaryotes. Cumulative experimental evidence about mitochondrial aconitases (Aco2) as one of the main targets of reactive oxygen and nitrogen species is generalized. The important role of Aco2 in maintenance of homeostasis of the intracellular iron pool and maintenance of the mitochondrial DNA is discussed. The role of Aco2 in the pathogenesis of some neurodegenerative diseases is highlighted. Inactivation or dysfunction of Aco2 as well as mutations found in the ACO2 gene appear to be significant factors in the development and promotion of various types of neurodegenerative diseases. A restoration of efficient mitochondrial functioning as a source of energy for the cell by targeting Aco2 seems to be one of the promising therapeutic directions to minimize progressive neurodegenerative disorders. Full article
(This article belongs to the Special Issue Mitochondrial Function in Human Health and Disease: 2nd Edition)
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