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Increased mitochondrial capacity due to chronic oxidative stress is reduced with age
Author(s) -
Marcinek David J,
Smith Steven R.,
Van Remmen Holly
Publication year - 2009
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.23.1_supplement.617.17
Subject(s) - mitochondrial biogenesis , oxidative stress , oxidative phosphorylation , mitochondrion , sod1 , electron transport chain , in vivo , superoxide dismutase , chemistry , mitochondrial ros , atp synthase , knockout mouse , endocrinology , biology , medicine , biochemistry , gene , genetics
Oxidative stress has been proposed to modulate mitochondrial function by reducing the coupling of oxidative phosphorylation (P/O) and inducing mitochondrial biogenesis. Here we test whether the effects of a chronic oxidative stress are age‐dependent. We compare in vivo mitochondrial metabolism and mitochondrial protein expression in wild‐type and Cu, Zn‐superoxide dismutase knockout mice (SOD1) at multiple ages. We used 31 P NMR and optical spectroscopies to measure ATP and O 2 fluxes in vivo . The 7‐month old SOD1 mice exhibited a significantly reduced mitochondrial P/O (P=0.05) and an increase in both maximal mitochondrial ATP production (ATP max ) (P=0.02) and O 2 consumption (VO 2max ) (P=0.01). The greater in vivo mitochondrial capacity in these mice was accompanied by increased expression of electron transport chain proteins. In contrast, in the 20‐month old mice there was no difference in P/O, ATP max , and VO 2max between the wild‐type and SOD1 genotypes. The effect of the SOD1 knockout on electron transport chain protein expression was also reduced in the 20‐month old mice. These data suggest that in young adults the chronic oxidative stress results in changes in mitochondrial metabolism that lead to increased mitochondrial capacity, whereas this response is reduced by 20 months. Supported by NIH grants AG028455, AG022385, and the Ellison Medical Foundation.