Age-related alterations in oxidatively damaged proteins of mouse heart mitochondrial electron transport chain complexes
Age-related alterations in oxidatively damaged proteins of mouse heart mitochondrial electron transport chain complexes
复制标题
DOI：
10.1016/j.freeradbiomed.2008.01.032
复制
发表时间：
2008-05-15
影响因子：
7.4
通讯作者：
Papaconstantinou, John
中科院分区：
文献类型：
--
作者：
Choksi, Kashyap B.;Papaconstantinou, John
线粒体产生的ROS随年龄增长而增加，是氧化修饰损伤蛋白质的主要因素。氧化损伤蛋白的积累被认为是与年龄相关的组织功能下降的一个原因。线粒体电子传递链(ETC)复合体I和III是产生ROS的主要部位，其复合亚单位的氧化修饰抑制了它们的体外活性。我们推测，线粒体复合体亚基可能是ROS修饰的主要靶点，这可能会损害正常的复合体活性。这项对年轻、中年和老年小鼠心脏线粒体的研究表明，复杂的I和V活性随着年龄的增长而下降，这与其亚单位的氧化修饰增加有关。数据还显示了ETC复合亚单位修饰的特异性，即几种蛋白质具有一种以上类型的加合物。我们推测，ETC复合体的电子泄漏会导致其亚单位的特异性损伤，并随着氧化损伤的积累而增加ROS的产生，导致进一步的线粒体功能障碍，这是一个循环过程，是衰老小鼠心脏生理功能进行性下降的基础。(C)2008 Elsevier Inc.保留所有权利。
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. (C) 2008 Elsevier Inc. All rights reserved.