Brand M D
MRC Dunn Human Nutrition Unit, Hills Road, CB2 2XY, Cambridge, UK.
Exp Gerontol. 2000 Sep;35(6-7):811-20. doi: 10.1016/s0531-5565(00)00135-2.
Mitochondria are incompletely coupled, and during oxidative phosphorylation some of the redox energy in substrates is lost as heat. Incomplete coupling is mostly due to a natural leak of protons across the mitochondrial inner membrane. In rat hepatocytes the futile cycle of proton pumping and proton leak is responsible for 20-25% of respiration; in perfused rat muscle the value is 35-50%. Mitochondrial proton cycling is estimated to cause 20-25% of basal metabolic rate in rats. Proton cycling is equally prominent in hepatocytes from several different mammalian and ectotherm species, so it may be a general pathway of ecologically significant energy loss in all aerobes. Because it occurs in ectotherms, thermogenesis cannot be its primary function. Instead, an attractive candidate for the function of the universal and expensive energy-dissipating proton cycle is to decrease the production of superoxide and other reactive oxygen species (ROS). This could be important in helping to minimise oxidative damage to DNA and in slowing ageing. Mitochondria are the major source of cellular ROS, and increased mitochondrial proton conductance leads to oxidation of ubiquinone and decreased ROS production in isolated mitochondria. However, to date there is no direct evidence in cells or organisms that mitochondrial proton cycling lowers ROS production or oxidative damage or that it increases lifespan.
线粒体的偶联是不完全的，在氧化磷酸化过程中，底物中的一些氧化还原能量以热量的形式损失。不完全偶联主要是由于质子自然地跨线粒体内膜泄漏。在大鼠肝细胞中，质子泵浦和质子泄漏的无效循环占呼吸作用的20% - 25%；在灌注的大鼠肌肉中，这一数值为35% - 50%。据估计，线粒体质子循环在大鼠基础代谢率中占20% - 25%。质子循环在几种不同的哺乳动物和变温动物物种的肝细胞中同样显著，因此它可能是所有需氧生物中具有生态意义的能量损失的普遍途径。由于它发生在变温动物中，产热不可能是其主要功能。相反，普遍且耗能的质子循环功能的一个有吸引力的候选者是减少超氧化物和其他活性氧（ROS）的产生。这对于帮助最小化对DNA的氧化损伤以及延缓衰老可能很重要。线粒体是细胞ROS的主要来源，线粒体质子传导性增加会导致泛醌氧化，并降低分离线粒体中的ROS产生。然而，迄今为止，在细胞或生物体中没有直接证据表明线粒体质子循环会降低ROS产生或氧化损伤，或者它会延长寿命。
