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.