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Oxidative stress leads to reduced coupling of oxidative phosphorylation in in vivo resting mouse skeletal muscle
Author(s) -
Siegel Michael,
Knowles Gary,
Harper MaryEllen,
Marcinek David
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1045.11
Subject(s) - oxidative stress , ucp3 , oxidative phosphorylation , reactive oxygen species , skeletal muscle , mitochondrion , mitochondrial ros , in vivo , chemistry , superoxide dismutase , uncoupling protein , biophysics , biology , medicine , biochemistry , endocrinology , microbiology and biotechnology , adipose tissue , brown adipose tissue
The “Uncoupling to Survive” Hypothesis suggests that oxidative stress induces reduced coupling of oxidative phosphorylation (P/O), which then reduces reactive oxygen species production by the mitochondria. This study sought to test whether oxidative stress leads to mitochondrial uncoupling in skeletal muscle in vivo . We subjected mice to two different doses of Paraquat (PARA), a redox cycling agent known to stimulate production of reactive oxygen species (ROS) in mitochondria. After two weeks of treatment, we used magnetic resonance spectroscopy to measure ATP flux and optical spectroscopy to measure oxygen uptake to determine the P/O value in the distal hind limb. PARA treatment led to a significant dose dependent decrease in mitochondrial P/O values in vivo (P<0.05), supporting the hypothesis that oxidative stress leads to mitochondrial uncoupling. We are currently investigating the mechanism of this reduced coupling using a UCP3 knockout mouse. Early results indicate no change in the coupling of resting skeletal muscle in the absence of UCP3. Studies are currently underway to determine if the presence of UCP3 is necessary for oxidative stress‐induced uncoupling in vivo. This work was supported by NIH grants AG022385 and AG028455 and the Ellison Medical Foundation.