Mitochondrial Dysfunction in Cardiovascular Aging
Mitochondrial Dysfunction in Cardiovascular Aging
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DOI：
10.1007/978-3-319-55330-6_24
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发表时间：
2017-01-01
期刊：
影响因子：
--
通讯作者：
Tandler, Bernard
中科院分区：
文献类型：
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作者：
Hoppel, Charles L.;Lesnefsky, Edward J.;Tandler, Bernard
线粒体是心肌细胞ATP的主要来源。线粒体代谢的损伤会导致现有蛋白质和DNA的损伤。这种有害影响是衰老过程的重要组成部分，降低了心肌细胞对抗压力的能力，如心肌梗死和随后的再灌注。在这种情况下，老年人心脏中的线粒体表现出氧化磷酸化减少，ATP产生减少，净活性氧产生增加；在这些情况下，所有这些影响都与线粒体数量的减少无关。这些缺陷几乎完全局限于位于肌原纤维（纤维间线粒体）之间的细胞器，而不是与线粒体种群总体相关。在复合体III和IV中，这些功能失调的方面表现出来。在明显纠正线粒体代谢缺陷的努力中，受影响的细胞器在一定程度上被线粒体自噬消除；与此同时，新的、未受影响的细胞器由线粒体的裂变产生。由于这些心脏健康问题定位于特定的线粒体，这些细胞器为可能有利地影响心脏衰老过程的治疗方法提供了潜在的靶点。
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 populationin 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.