title: Age-related alterations in oxidatively damaged proteins of mouse heart mitochondrial electron transport chain complexes.
abstract: Mitochondrially generated ROS increase with age and are a major factor that damages proteins by oxidative modification. Accumulation of oxidatively damaged proteins has been implicated as a causal factor in the age-associated decline in tissue function. Mitochondrial electron transport chain (ETC) complexes I and III are the principle sites of ROS production, and oxidative modifications to their complex subunits inhibit their in vitro activity. We hypothesize that mitochondrial complex subunits may be primary targets for modification by ROS, which may impair normal complex activity. This study of heart mitochondria from young, middle-aged, and old mice reveals that there is an age-related decline in complex I and V activity that correlates with increased oxidative modification to their subunits. The data also show a specificity for modifications of the ETC complex subunits, i.e., several proteins have more than one type of adduct. We postulate that the electron leakage from ETC complexes causes specific damage to their subunits and increased ROS generation as oxidative damage accumulates, leading to further mitochondrial dysfunction, a cyclical process that underlies the progressive decline in physiologic function of the aged mouse heart.
authors.affiliation: Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555-0643, USA.
authors.forename: Kashyap B
authors.initials: KB
authors.lastname: Choksi
authors.forename: John
authors.initials: J
authors.lastname: Papaconstantinou
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D004579:Electron Transport / Q000502:physiology; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008929:Mitochondria, Heart / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D020543:Proteome / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D045222:Electron Transport Chain Complex Proteins; D020543:Proteome; D017382:Reactive Oxygen Species