The organization of mitochondrial supercomplexes is modulated by oxidative stress in vivo in mouse models of mitochondrial encephalopathy

Mir R. Anwar, Amy Saldana-Caboverde, Sofia Garcia, Francisca Diaz

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

We examine the effect of oxidative stress on the stability of mitochondrial respiratory complexes and their association into supercomplexes (SCs) in the neuron-specific Rieske iron sulfur protein (RISP) and COX10 knockout (KO) mice. Previously we reported that these two models display different grades of oxidative stress in distinct brain regions. Using blue native gel electrophoresis, we observed a redistribution of the architecture of SCs in KO mice. Brain regions with moderate levels of oxidative stress (cingulate cortex of both COX10 and RISP KO and hippocampus of the RISP KO) showed a significant increase in the levels of high molecular weight (HMW) SCs. High levels of oxidative stress in the piriform cortex of the RISP KO negatively impacted the stability of CI, CIII and SCs. Treatment of the RISP KO with the mitochondrial targeted antioxidant mitoTEMPO preserved the stability of respiratory complexes and formation of SCs in the piriform cortex and increased the levels of glutathione peroxidase. These results suggest that mild to moderate levels of oxidative stress can modulate SCs into a more favorable architecture of HMW SCs to cope with rising levels of free radicals and cover the energetic needs.

Original languageEnglish (US)
Article number1582
JournalInternational journal of molecular sciences
Volume19
Issue number6
DOIs
StatePublished - Jun 2018

Keywords

  • Antioxidants
  • Blue native gel electrophoresis
  • COX10
  • Complex III
  • Complex IV
  • Mitochondrial supercomplexes
  • Oxidative phosphorylation
  • Rieske iron sulfur protein

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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