Hoppel Charles L, Lesnefsky Edward J, Chen Qun, Tandler Bernard
Department of Pharmacology, Case Western Reserve University, School of Medicine, Cleveland, OH, 44106, USA.
Department of Medicine, Case Western Reserve University, School of Medicine, Cleveland, OH, 44106, USA.
Adv Exp Med Biol. 2017;982:451-464. doi: 10.1007/978-3-319-55330-6_24.
Mitochondria are the prime source of ATP in cardiomyocytes. Impairment of mitochondrial metabolism results in damage to existing proteins and DNA. Such deleterious effects are part and parcel of the aging process, reducing the ability of cardiomyocytes to counter stress, such as myocardial infarction and consequent reperfusion. In such conditions, mitochondria in the heart of aged individuals exhibit decreased oxidative phosphorylation, decreased ATP production, and increased net reactive oxygen species production; all of these effects are independent of the decrease in number of mitochondria that occurs in these situations. Rather than being associated with the mitochondrial population in toto, these defects are almost exclusively confined to those organelles positioned between myofibrils (interfibrillar mitochondria). It is in complex III and IV where these dysfunctional aspects are manifested. In an apparent effort to correct mitochondrial metabolic defects, affected organelles are to some extent eliminated by mitophagy; at the same time, new, unaffected organelles are generated by fission of mitochondria. Because these cardiac health issues are localized to specific mitochondria, these organelles offer potential targets for therapeutic approaches that could favorably affect the aging process in heart.
线粒体是心肌细胞中ATP的主要来源。线粒体代谢受损会导致现有蛋白质和DNA受损。这些有害影响是衰老过程的一部分，会降低心肌细胞应对压力（如心肌梗死及随后的再灌注）的能力。在这种情况下，老年个体心脏中的线粒体表现出氧化磷酸化降低、ATP生成减少以及净活性氧生成增加；所有这些影响都与这些情况下线粒体数量的减少无关。这些缺陷并非与整个线粒体群体相关，几乎完全局限于位于肌原纤维之间的那些细胞器（肌原纤维间线粒体）。这些功能障碍方面在复合物III和IV中表现出来。为了明显纠正线粒体代谢缺陷，受影响的细胞器在一定程度上会通过线粒体自噬被清除；与此同时，新的未受影响的细胞器通过线粒体分裂产生。由于这些心脏健康问题局限于特定的线粒体，这些细胞器为可能对心脏衰老过程产生有利影响的治疗方法提供了潜在靶点。
