Open AccessMnSOD deficiency results in elevated oxidative stress and decreased mitochondrial function but does not lead to muscle atrophy during aging
Author(s) -
Lustgarten Michael S.,
Jang Youngmok C.,
Liu Yuhong,
Qi Wenbo,
Qin Yuejuan,
Dahia Patricia L.,
Shi Yun,
Bhattacharya Arunabh,
Muller Florian L.,
Shimizu Takahiko,
Shirasawa Takuji,
Richardson Arlan,
Van Remmen Holly
Publication year - 2011
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/j.1474-9726.2011.00695.x
Subject(s) - oxidative stress , medicine , endocrinology , biology , mitochondrion , skeletal muscle , atrophy , aconitase , muscle atrophy , oxidative phosphorylation , citrate synthase , sarcopenia , mitochondrial ros , biochemistry , enzyme
Summary In a previous study, we reported that a deficiency in MnSOD activity (approximately 80% reduction) targeted to type IIB skeletal muscle fibers was sufficient to elevate oxidative stress and to reduce muscle function in young adult mice ( TnIFastCreSod2 fl/fl mice). In this study, we used TnIFastCreSod2 fl/fl mice to examine the effect of elevated oxidative stress on mitochondrial function and to test the hypothesis that elevated oxidative stress and decreased mitochondrial function over the lifespan of the TnIFastCreSod2 fl/fl mice would be sufficient to accelerate muscle atrophy associated with aging. We found that mitochondrial function is reduced in both young and old TnIFastCreSod2 fl/fl mice, when compared with control mice. Complex II activity is reduced by 47% in young and by approximately 90% in old TnIFastCreSod2 fl/fl mice, and was found to be associated with reduced levels of the catalytic subunits for complex II, SDHA and SDHB. Complex II‐linked mitochondrial respiration is reduced by approximately 70% in young TnIFastCreSod2 fl/fl mice. Complex II‐linked mitochondrial Adenosine‐Tri‐Phosphate (ATP) production is reduced by 39% in young and was found to be almost completely absent in old TnIFastCreSod2 fl/fl mice. Furthermore, in old TnIFastCreSod2 fl/fl mice, aconitase activity is almost completely abolished; mitochondrial superoxide release remains > 2‐fold elevated; and oxidative damage (measured as F 2 ‐ isoprostanes) is increased by 30% relative to age‐matched controls. These data show that despite elevated skeletal muscle–specific mitochondrial oxidative stress, oxidative damage, and complex II‐linked mitochondrial dysfunction, age‐related muscle atrophy was not accelerated in old TnIFastCreSod2 fl/fl mice, suggesting mitochondrial oxidative stress may not be causal for age‐related muscle atrophy.