The role of the electron transport gene SDHC on lifespan and cancer.
Much attention has been focused on the hypothesis that oxidative damage contributes to cellular and organismal aging. A mev-1 mutation in the cytochrome b large subunit (SDHC) of complex II results in superoxide anion (O(2)(-)) overproduction and therefore leads to apoptosis and precocious aging in the nematode Caenorhabditis elegans. To extend these data, a transgenic mouse cell line was constructed with a homologous mutation to mev-1. Many of the mutant nematode phenotypes (e.g., increased superoxide anion production, apoptosis) were recapitulated in the mouse. In addition, a significant fraction of the cells that survived apoptosis were transformed. These data support the notion that oxidative stress from mitochondria play an important role of both apoptosis, which leads to precocious aging, and cancer.
Ishii
Naoaki
N
Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan. nishii@is.icc.u-tokai.ac.jp
Ishii
Takamasa
T
Hartman
Philip S
PS
D016475:3T3 Cells; D000375:Aging / Q000235:genetics*; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D045303:Cytochromes b; D042963:Electron Transport Complex II / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008136:Longevity / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009369:Neoplasms / Q000235:genetics*; D018384:Oxidative Stress / Q000235:genetics; D013385:Succinate Dehydrogenase / Q000235:genetics; D013481:Superoxides / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; C472666:MEV-1 protein, C elegans; D008565:Membrane Proteins; C108096:SDHC protein, human; D013481:Superoxides; D045303:Cytochromes b; D042963:Electron Transport Complex II; D013385:Succinate Dehydrogenase