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Mitochondria co‐opt exercise adaptations in defense against oxidative stress in vivo
Author(s) -
Conley Kevin,
Jubrias Sharon,
Siegel Michael,
Syrjala Karen,
Remmen Holly,
Aylward Elizabeth,
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.801.20
Subject(s) - oxidative stress , mitochondrion , reactive oxygen species , oxidative phosphorylation , mitochondrial ros , microbiology and biotechnology , sod1 , mitochondrial biogenesis , cellular respiration , superoxide dismutase , chemistry , biology , biochemistry
Reactive oxygen species (ROS) are implicated in oxidative damage but at low levels act as signals, especially in exercise. Here we show that the mitochondrial defense against ROS emulates the impact of exercise. Innovative spectroscopic tools applied to muscles in vivo found two key cell changes in a mouse model of the knockout of a key antioxidant defense, Cu,Zn‐superoxide dismutase (SOD1 −/−). These changes were paralleled in two human conditions with oxidative stress but prior to development of oxidative damage (pre‐symptomatic Huntington's disease and cancer survivors). First is an increase in mitochondrial uncoupling (reduced ATP per O 2 ) that raises respiration. Dissipating the mitochondrial membrane potential causes uncoupling and is implicated as a negative feedback mechanism that counteracts elevated ROS but comes at the cost of greater O 2 uptake. Second is a mobilization of metabolism. Uncoupling not only elevates respiration but also cellular AMP level, which increases substrate supply and activates mitochondrial biogenesis to raise oxidative capacity of muscle. Thus mitochondria are the first line of defense in response to elevated ROS with a series of compensatory cellular changes that ameliorate the impact of oxidative stress and activate cellular metabolism in a manner similar to the effect of exercise. Supported by AG028455, AR041928, AR036606, CA103728 and the CHDI Foundation.