Di Lisa Fabio, Bernardi Paolo
Dipartimento di Chimica Biologica, Università di Padova, Viale G. Colombo 3, 35121 Padova, Italy.
Cardiovasc Res. 2005 May 1;66(2):222-32. doi: 10.1016/j.cardiores.2005.02.009.
Mitochondria have been suggested to be causally linked to age-related alterations through respiratory chain dysfunction and formation of reactive oxygen species, leading to damage of mitochondrial DNA. Impaired biosynthesis of respiratory chain and ATP synthase subunits encoded by mitochondrial genes would set up a vicious cycle contributing to the aging process. Mitochondria are also involved in the increased susceptibility to ischemic injury observed in aged hearts, a process where the mitochondrial permeability transition pore (PTP) may play a role. Here, we analyze (i) the possible mechanisms through which PTP opening might contribute to age-related myocardial alterations; (ii) the available evidence of an increased probability of PTP opening in mitochondria isolated from aged tissues; (iii) the current methodological limitations that complicate the elucidation of causal relationships between PTP opening, mitochondrial dysfunction, and myocardial aging.
线粒体被认为通过呼吸链功能障碍和活性氧的形成与年龄相关的改变存在因果联系，进而导致线粒体DNA损伤。线粒体基因编码的呼吸链和ATP合酶亚基的生物合成受损会形成一个恶性循环，促进衰老过程。线粒体还与老年心脏中观察到的对缺血性损伤易感性增加有关，在这个过程中，线粒体通透性转换孔（PTP）可能发挥作用。在此，我们分析：（i）PTP开放可能导致年龄相关心肌改变的潜在机制；（ii）从老年组织分离的线粒体中PTP开放概率增加的现有证据；（iii）目前使阐明PTP开放、线粒体功能障碍和心肌衰老之间因果关系变得复杂的方法学局限性。
