Age-related increase in mitochondrial proton leak and decrease in ATP turnover reactions in mouse hepatocytes
Age-related increase in mitochondrial proton leak and decrease in ATP turnover reactions in mouse hepatocytes
复制标题
DOI：
10.1152/ajpendo.1998.275.2.e197
复制
发表时间：
1998-08-01
影响因子：
5.1
通讯作者：
Weindruch, R
中科院分区：
文献类型：
--
作者：
Harper, ME;Monemdjou, S;Weindruch, R
线粒体中与氧化磷酸化相关的变化，包括呼吸控制率降低和线粒体内膜脂质组成改变，使我们研究了老年（30个月）和年轻（3个月）雄性C57 BL/J小鼠肝细胞中的氧化磷酸化。自上而下的代谢控制分析及其扩展，弹性分析，被用来确定的控制和调节的三个块的反应构成氧化磷酸化系统的变化：底物氧化，线粒体质子泄漏，和ATP周转反应。老年小鼠细胞的静息耗氧量比年轻细胞低15%（P < 0.05）。这完全可以通过支持ATP周转反应的耗氧量减少来解释。在评估的所有线粒体膜电位值下，用于平衡泄漏的总耗氧量的比例在老细胞中比在年轻细胞中更大。代谢控制系数表明，控制呼吸和磷酸化远离底物氧化增加控制泄漏和ATP周转反应的转变。对于ATP周转和泄漏反应消耗的每个氧原子，线粒体合成的ATP分子的实际数量的控制在老年细胞中比在年轻细胞中更大，表明老年细胞的效率对这两个反应块的变化比年轻细胞更敏感。
Age-related changes in mitochondria, including decreased respiratory control ratios and altered mitochondrial inner membrane lipid composition, led us to study oxidative phosphorylation in hepatocytes from old (30 mo) and young (3 mo) male C57BL/J mice. Top-down metabolic control analysis and its extension, elasticity analysis, were used to identify changes in the control and regulation of the three blocks of reactions constituting the oxidative phosphorylation system: substrate oxidation, mitochondrial proton leak, and the ATP turnover reactions. Resting oxygen consumption of cells from old mice was 15% lower (P < 0.05) than in young cells. This is explained entirely by a decrease in oxygen consumption supporting ATP turnover reactions. At all values of mitochondrial membrane potential assessed, the proportion of total oxygen consumption used to balance the leak was greater in the old cells than in the young cells. Metabolic control coefficients indicate a shift in control over respiration and phosphorylation away from substrate oxidation toward increased control by leak and by ATP turnover reactions. Control of the actual number of ATP molecules synthesized by mitochondria for each oxygen atom consumed by the ATP turnover and leak reactions was greater in old than in young cells, showing that efficiency in older cells is more sensitive to changes in these two blocks of reactions than in young cells.