Mitochondrial DNA Damage: Role of Ogg1 and Aconitase

摘要: Mitochondria have a vital role in respiration-coupled energy production, amino acid and fatty metabolism, Fe2+/Ca2+ homeostasis the integration of apoptotic signals that regulate cellular life death (Babcock et al., 1997; Loeb 2005; Taylor & Turnbull, Kroemer 2007). Given importance these functions regulated by mitochondria with implications for aging, degenerative diseases carcinogenesis, it is not surprising this organelle has been subject intensive investigation decades continues to challenge investigators. produce nearly 90% all made body oxidative phosphorylation occurs via electron transport chain (ETC). are major site reactive oxygen species (ROS) production. It estimated 1–5% consumed mitochondrial ETC converted ROS (Kroemer Mammalian covalently closed round DNA (mtDNA) replicated expressed within close proximity potentially damaging (Clayton 1982; Clayton 1984; mtDNA contains 37 genes encode 13 proteins (all which involved ETC), 22 tRNAs, 2 rRNAs (Anderson 1981). The remaining proteins, metabolic enzymes, RNA polymerases ribosomal encoded nuclear genome. Oxidative stress-induced damage implicated wide range pathologic processes including aging various organs tissues (Bohr 2002; Van Houten 2006; 2007; Gredilla 2010). In review, we summarize evidence augments mitochondriaregulated (intrinsic) apoptosis; an event underlies pathophysiologic mechanisms diverse diseases. We focus our attention on one form stress, exposure asbestos fibers, well known cause pulmonary fibrosis (asbestosis) malignancies (e.g. mesothelioma lung cancer). Specifically, examine repair enzyme (8-oxoguanine glycosylase; Ogg1) recently described novel mechanism whereby Ogg1 acts as aconitase chaperone protein prevent oxidant-induced alveolar epithelial cell (AEC) dysfunction intrinsic apoptosis. discuss studies showing