H2O2-induced mitochondrial fragmentation in C2C12 myocytes

In skeletal muscle and many other cell types mitochondria exist as an elaborate and dynamic network in which individual mitochondi la 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 C2C12 mouse myocytes we show that acute exposure to the reactive oxygen species (ROS) hydiogen peroxide (H2O2) induces a slow fragmentation of the mitochondrial reticulum that is reversible over 24 h Although H2O2 decomposes rapidly in culture medium the full extent of fragmentation occurs 5-6 h posttreatment suggesting that H2O2 affects mitochondrial morphology by modulating cellular physiology Supraphysiolo gical (>1 mM) concentrations of H2O2 are cytotoxic but lower concentiations (250 mu M) sufficient to Induce transient fragmentation do not lower cell viability H2O2-induced maochondnal fragmentation is preceded by decreases in inner mitochondrial membrane potential and maximal respiratory rate suggesting a possible mechanism Because H2O2 is produced in contracting muscle our results raise the possibility that ROS generation may contribute to exercise induced changes in mitochonchial morphology in vivo (C) 2010 Elsevier Inc All rights reserved