Increased mitochondrial matrix-directed superoxide production by fatty acid hydroperoxides in skeletal muscle mitochondria

Arunabh Bhattacharya, Michael Lustgarten, Yun Shi, Yuhong Liu, Youngmok C. Jang, Daniel Pulliam, Amanda L. Jernigan, Holly Van Remmen

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Previous studies have shown that muscle atrophy is associated with mitochondrial dysfunction and an increased rate of mitochondrial reactive oxygen species production. We recently demonstrated that fatty acid hydroperoxides (FA-OOHs) are significantly elevated in mitochondria isolated from atrophied muscles. The purpose of this study was to determine whether FA-OOHs can alter skeletal muscle mitochondrial function. We found that FA-OOHs (at low-micromolar concentrations) induce mitochondrial dysfunction assessed by a decrease in the rate of ATP production, oxygen consumption, and activity of respiratory chain complexes I and III. Using methods to distinguish superoxide release toward the matrix and toward the intermembrane space, we demonstrate that FA-OOHs significantly elevate oxidative stress in the mitochondrial matrix (and not the intermembrane space), with complex I as the major site of superoxide production (most probably from a site upstream of the ubiquinone binding site but downstream from the flavin binding site-the iron sulfur clusters). Our results are the first to indicate that FA-OOHs are important modulators of mitochondrial function and oxidative stress in skeletal muscle mitochondria and may play an important role in muscle atrophies that are associated with increased generation of FA-OOHs, e.g., denervation-induced muscle atrophy.

Original languageEnglish (US)
Pages (from-to)592-601
Number of pages10
JournalFree Radical Biology and Medicine
Volume50
Issue number5
DOIs
StatePublished - Mar 1 2011

Keywords

  • Fatty acid hydroperoxides
  • Free radicals
  • Hydrogen peroxide
  • Mitochondria
  • Oxidative stress
  • Superoxide

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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