Tummino P J, Gafni A
Institute of Gerontology, University of Michigan, Ann Arbor 48109.
Mech Ageing Dev. 1991 Jun 14;59(1-2):177-88. doi: 10.1016/0047-6374(91)90083-c.
This study was undertaken to compare the rates of succinate-supported hepatic mitochondrial respiration between 12 months (adult) and 29 months (old) male Fischer 344 rats. Experiments were also performed to determine the activity of adenine nucleotide translocase and the effect of its inhibition on mitochondrial respiration. Succinate-supported state 3 mitochondrial respiration was found to decline 20% between 12 and 29 months of age in rat liver, along with a similar 25% decrease in the respiratory control ratio with age. Adenine nucleotide translocase activity is shown to decrease 39% from adult to old rat liver mitochondria. This decrease does not, however, account for the decline in state 3 respiration, since translocase activity is approximately 50% greater than state 3 respiration in both adult and old rats. Therefore, adenine nucleotide translocase is not rate-limiting for state 3 mitochondrial respiration. Neither the rate of succinate permeation into the mitochondrial nor the rate of electron transport is rate-limiting for state 3 respiration, indicated by the greatly increased oxygen consumption with addition of the uncoupler carbonyl cyanide m-chlorophenyl hydrazone (m-CCCP). These processes, therefore, are not responsible for the observed decline in state 3 respiration. The implications and possible cause of the age-related decrease in the maximal rate of ATP-synthesis are discussed.
本研究旨在比较12个月大（成年）和29个月大（老年）雄性Fischer 344大鼠之间琥珀酸支持的肝线粒体呼吸速率。还进行了实验以确定腺嘌呤核苷酸转位酶的活性及其抑制对线粒体呼吸的影响。发现大鼠肝脏中，12至29个月龄期间，琥珀酸支持的线粒体状态3呼吸下降了20%，呼吸控制率也随年龄下降了25%左右。从成年大鼠到老年大鼠肝脏线粒体，腺嘌呤核苷酸转位酶活性下降了39%。然而，这种下降并不能解释状态3呼吸的下降，因为在成年和老年大鼠中，转位酶活性都比状态3呼吸大约高50%。因此，腺嘌呤核苷酸转位酶不是状态3线粒体呼吸的限速因素。添加解偶联剂间氯苯腙（m-CCCP）后耗氧量大幅增加，这表明琥珀酸进入线粒体的速率和电子传递速率都不是状态3呼吸的限速因素。因此，这些过程不是观察到的状态3呼吸下降的原因。本文讨论了与年龄相关的ATP合成最大速率下降的影响和可能原因。
