Title | H2O2-induced mitochondrial fragmentation in C2C12 myocytes. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Authors | Fan X, Hussien R, Brooks GA |
Journal | Free Radic Biol Med |
Volume | 49 |
Issue | 11 |
Pagination | 1646-54 |
Date Published | 2010 Dec 01 |
ISSN | 1873-4596 |
Keywords | Animals, Cell Line, Cell Respiration, Cell Survival, Hydrogen Peroxide, Membrane Potential, Mitochondrial, Mice, Mitochondria, Muscle, Muscle Fibers, Skeletal, Oxidative Stress, Reactive Oxygen Species, Temperature, Time Factors |
Abstract | In skeletal muscle and many other cell types, mitochondria exist as an elaborate and dynamic network in which "individual" mitochondria exist only transiently even under nonstimulated conditions. The balance of continuous mitochondrial fission and fusion defines the morphology of the mitochondrial reticulum. Environmental stimuli, such as oxidative stress, can influence fusion and fission rates, resulting in a transformation of the network's connectivity. Using confocal laser scanning microscopy of C(2)C(12) mouse myocytes, we show that acute exposure to the reactive oxygen species (ROS) hydrogen peroxide (H(2)O(2)) induces a slow fragmentation of the mitochondrial reticulum that is reversible over 24h. Although H(2)O(2) decomposes rapidly in culture medium, the full extent of fragmentation occurs 5-6h posttreatment, suggesting that H(2)O(2) affects mitochondrial morphology by modulating cellular physiology. Supraphysiological (>1 mM) concentrations of H(2)O(2) are cytotoxic, but lower concentrations (250 μM) sufficient to induce transient fragmentation do not lower cell viability. H(2)O(2)-induced mitochondrial fragmentation is preceded by decreases in inner mitochondrial membrane potential and maximal respiratory rate, suggesting a possible mechanism. Because H(2)O(2) is produced in contracting muscle, our results raise the possibility that ROS generation may contribute to exercise-induced changes in mitochondrial morphology in vivo. |
DOI | 10.1016/j.freeradbiomed.2010.08.024 |
Alternate Journal | Free Radic. Biol. Med. |
PubMed ID | 20801212 |
PubMed Central ID | PMC2970628 |
Grant List | R01 AR050459 / AR / NIAMS NIH HHS / United States R01 AR050459-04 / AR / NIAMS NIH HHS / United States AR050459 / AR / NIAMS NIH HHS / United States |
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