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The Electron Transport Chain01:30

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Inner Mitochondrial Membrane Sensitivity to Na+ Reveals Partially Segmented Functional CoQ Pools
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Cells lacking Rieske iron-sulfur protein have a reactive oxygen species-associated decrease in respiratory complexes

Francisca Diaz1, José Antonio Enríquez, Carlos T Moraes

  • 1Department of Neurology, University of Miami, Miller School of Medicine, Miami, Florida, USA. FDiaz1@med.miami.edu

Molecular and Cellular Biology
|November 23, 2011
PubMed
Summary

Mitochondrial supercomplexes are affected by defective CIII function. Reactive oxygen species (ROS) regulate the stability of respiratory complexes and supercomplexes in cells with impaired oxidative phosphorylation.

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Area of Science:

  • Mitochondrial biology
  • Cellular respiration
  • Biochemistry

Background:

  • Mitochondrial respiratory complexes (CI, CIII, CIV) form supercomplexes.
  • The Rieske iron-sulfur protein (RISP) is a catalytic subunit of CIII.
  • RISP deficiency impacts CIII assembly and function.

Purpose of the Study:

  • To investigate the assembly and stability of respiratory supercomplexes in RISP-deficient cells.
  • To determine the role of reactive oxygen species (ROS) in regulating mitochondrial supercomplexes under defective oxidative phosphorylation.

Main Methods:

  • Analysis of respiratory complex assembly in RISP knockout (KO) mouse lung fibroblasts.
  • Assessment of CIII activity and supercomplex levels upon RISP reintroduction.
  • Investigating the effects of hypoxia and oxidative phosphorylation inhibitors on supercomplexes.
  • Evaluating the impact of superoxide dismutase (SOD) mimetic and SOD2 overexpression.

Main Results:

  • RISP deficiency leads to assembly of non-functional CIII precomplexes and decreased levels of CI, CIV, and supercomplexes.
  • Restoration of RISP rescues CIII activity and increases CI, CIV, and supercomplex levels.
  • Hypoxia partially restores CI, CIV, and supercomplex assembly in RISP KO cells.
  • ROS-generating OXPHOS inhibitors reduce CI and supercomplex levels.
  • SOD mimetic and SOD2 overexpression partially increase supercomplex levels in RISP KO cells.

Conclusions:

  • RISP is crucial for CIII activity and the stability of CI, CIV, and supercomplexes.
  • Reactive oxygen species (ROS) play a regulatory role in the stability of mitochondrial supercomplexes, particularly in the context of impaired oxidative phosphorylation.