Role of oxidative stress from mitochondria on aging and cancer.
Much attention has been focused on the hypothesis that oxidative damage plays a part in cellular and organismal aging. Oxygen is initially converted to superoxide anion (O2), one of the reactive oxygen species (ROS), by electrons mainly leaked from complex III in the electron transport system present in mitochondria, where it is the major endogenous source of ROS. We have shown that a mutation in a subunit, cytochrome b large subunit (SDHC), of complex II, also results in increasing O2 production and therefore leads to apoptosis and precocious aging in Caenorhabditis elegans. Recently, individuals with an inherited propensity for vascularized head and neck tumors (ie, paragangliomas) have been shown to possess one of several mutations in complex II. To further explore the role of oxidative stress from mitochondria on apoptosis and cancer, we established a transgenic cell line with a point mutation at the ubiquinone binding region in the SDHC gene. As expected, this mutation increased O2 production from complex II and led to excess apoptosis. Moreover, a significant fraction of the surviving cells from the apoptosis were transformed, as evidenced by increased tumor formation, after injection into mice. Oxidative stress results in damage to the cellular components including mitochondria and therefore leads to apoptosis. Furthermore, oxidative stress seems to cause mutations in DNA and leads to cancer. It is suggested that oxidative stress from mitochondria plays an important role in 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
D000375:Aging / Q000378:metabolism*; D000818:Animals; D004734:Energy Metabolism / Q000502:physiology; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism
D017382:Reactive Oxygen Species