Mitochondrial oxidative stress causes mitochondrial fragmentation via differential modulation of mitochondrial fission-fusion proteins

FEBS J. 2011 Apr;278(6):941-54. doi: 10.1111/j.1742-4658.2011.08010.x. Epub 2011 Feb 3.


Mitochondria are dynamic organelles that undergo continual fusion and fission to maintain their morphology and functions, but the mechanism involved is still not clear. Here, we investigated the effect of mitochondrial oxidative stress triggered by high-fluence low-power laser irradiation (HF-LPLI) on mitochondrial dynamics in human lung adenocarcinoma cells (ASTC-a-1) and African green monkey SV40-transformed kidney fibroblast cells (COS-7). Upon HF-LPLI-triggered oxidative stress, mitochondria displayed a fragmented structure, which was abolished by exposure to dehydroascorbic acid, a reactive oxygen species scavenger, indicating that oxidative stress can induce mitochondrial fragmentation. Further study revealed that HF-LPLI caused mitochondrial fragmentation by inhibiting fusion and enhancing fission. Mitochondrial translocation of the profission protein dynamin-related protein 1 (Drp1) was observed following HF-LPLI, demonstrating apoptosis-related activation of Drp1. Notably, overexpression of Drp1 increased mitochondrial fragmentation and promoted HF-LPLI-induced apoptosis through promoting cytochrome c release and caspase-9 activation, whereas overexpression of mitofusin 2 (Mfn2), a profusion protein, caused the opposite effects. Also, neither Drp1 overexpression nor Mfn2 overexpression affected mitochondrial reactive oxygen species generation, mitochondrial depolarization, or Bax activation. We conclude that mitochondrial oxidative stress mediated through Drp1 and Mfn2 causes an imbalance in mitochondrial fission-fusion, resulting in mitochondrial fragmentation, which contributes to mitochondrial and cell dysfunction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology
  • COS Cells
  • Caspase 9 / metabolism
  • Cell Line, Tumor
  • Chlorocebus aethiops
  • Cytochromes c / metabolism
  • Dynamins
  • GTP Phosphohydrolases / metabolism
  • Humans
  • Lasers
  • Membrane Proteins / biosynthesis
  • Microtubule-Associated Proteins / metabolism
  • Mitochondria / physiology*
  • Mitochondria / radiation effects
  • Mitochondria / ultrastructure
  • Mitochondrial Proteins / biosynthesis
  • Mitochondrial Proteins / metabolism*
  • Oxidative Stress
  • Reactive Oxygen Species / metabolism*


  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Mitochondrial Proteins
  • Reactive Oxygen Species
  • Cytochromes c
  • Caspase 9
  • GTP Phosphohydrolases
  • MFN2 protein, human
  • DNM1L protein, human
  • Dynamins