Author(s): GarcaRuiz I, FernndezMoreira D, SolsMuoz P, RodrguezJuan C, DazSanjun T,
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Abstract We investigate the cause of the low activity of mitochondrial complex I found in ob/ob mice with nonalcoholic fatty liver disease. In mitochondrial proteins from ob/ob mice, we assessed complex I activity, fully assembled complex I, and its subunits, oxygen consumption, gene expression of complex I subunits, and oxidative damage to DNA. In mitochondrial proteins from the liver of ob/ob mice, complex I activity, fully assembly of this complex and complex I subunits were markedly reduced. Likewise, gene expression of mitochondrial DNA-encoded subunits was significantly decreased in obese mice, but not nuclear DNA-encoded subunits. Treatment of obese mice with uric acid, anti-TNFalpha antibody or a mimic of manganese superoxide dismutase normalized all these abnormalities. "In vitro" addition of peroxynitrite to mitochondrial proteins from wild-type mice reproduced the abnormalities found in ob/ob mice (decreased complex I activity, the amount of fully assembled complex I, and its subunits, and mitochondrial oxygen consumption). Low activity of complex I found in ob/ob mice can be ascribed to a reduced amount of fully assembled complex, which may be attributed to degradation and reduced synthesis of its subunits by peroxynitrite. Exposure of mitochondrial proteins from normal mice to peroxynitrite reproduced the proteomic abnormalities present in ob/ob mice.
This article was published in J Proteome Res
and referenced in Journal of Kidney