Oxidative stress-induced mitochondrial fragmentation and movement in skeletal muscle myoblasts

Am J Physiol Cell Physiol. 2014 Jun 15;306(12):C1176-83. doi: 10.1152/ajpcell.00017.2014. Epub 2014 Apr 16.

Abstract

Mitochondria are dynamic organelles, capable of altering their morphology and function. However, the mechanisms governing these changes have not been fully elucidated, particularly in muscle cells. We demonstrated that oxidative stress with H2O2 resulted in a 41% increase in fragmentation of the mitochondrial reticulum in myoblasts within 3 h of exposure, an effect that was preceded by a reduction in membrane potential. Using live cell imaging, we monitored mitochondrial motility and found that oxidative stress resulted in a 30% reduction in the average velocity of mitochondria. This was accompanied by parallel reductions in both organelle fission and fusion. The attenuation in mitochondrial movement was abolished by the addition of N-acetylcysteine. To investigate whether H2O2-induced fragmentation was mediated by dynamin-related protein 1, we incubated cells with mDivi1, an inhibitor of dynamin-related protein 1 translocation to mitochondria. mDivi1 attenuated oxidative stress-induced mitochondrial fragmentation by 27%. Moreover, we demonstrated that exposure to H2O2 upregulated endoplasmic reticulum-unfolded protein response markers before the initiation of mitophagy signaling and the mitochondrial-unfolded protein response. These findings indicate that oxidative stress is a vital signaling mechanism in the regulation of mitochondrial morphology and motility.

Keywords: mitochondria; mitochondrial morphology; mitochondrial movement; oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Line
  • Dynamins / biosynthesis
  • Dynamins / metabolism
  • Hydrogen Peroxide / toxicity
  • Mice
  • Mitochondria, Muscle / drug effects*
  • Mitochondria, Muscle / physiology
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / physiology
  • Myoblasts / drug effects*
  • Myoblasts / physiology
  • Oxidative Stress / drug effects*
  • Oxygen Consumption
  • Reactive Oxygen Species / metabolism
  • Reticulum / drug effects
  • Reticulum / metabolism

Substances

  • Reactive Oxygen Species
  • Hydrogen Peroxide
  • Dnm1l protein, mouse
  • Dynamins