Stefano George B, Bjenning Christina, Wang Fuzhou, Wang Nan, Kream Richard M
International Scientific Information, Inc., 150 Broadhollow Rd, Ste 114, Melville, NY, 11747, USA.
Cardiometabolic Designs LLC, 160 W15th Ave, Suite 303, Sea Cliff, NY, 11579, USA.
Adv Exp Med Biol. 2017;982:577-594. doi: 10.1007/978-3-319-55330-6_30.
Genetic polymorphisms, in concert with well-characterized etiology and progression of major pathologies, plays a significant role in aberrant processes afflicting human populations. Mitochondrial heteroplasmy represents a dynamically determined co-expression of inherited polymorphisms and somatic pathology in varying ratios within individual mitochondrial DNA (mtDNA) genomes with repetitive patterns of tissue specificity. The ratios of the MtDNA genomes represent a balance between healthy and pathological cellular outcomes. Mechanistically, cardiomyopathies have profound alterations of normative mitochondrial function. Certain allele imbalances in the nuclear mitochondrial genome are associated with key energy mitochondrial proteins. Mitochondrial heteroplasmy may manifest itself at critical protein expression points, e.g., cytochrome c oxidase (COX). Pathological mtDNA mutations also are associated with the development of congestive heart failure. Interestingly, mitochondrial 'normal vs. abnormal' ratios of various heteroplasmic populations may occur in families. In the translational context of human health and disease, we discuss the need for determining critical foci to probe multiple biological roles of mitochondrial heteroplasmy in cardiomyopathy.
基因多态性与主要病理特征明确的病因和进展协同作用，在困扰人类群体的异常过程中发挥着重要作用。线粒体异质性代表了个体线粒体DNA（mtDNA）基因组中遗传多态性和体细胞病理以不同比例动态确定的共表达，具有组织特异性的重复模式。mtDNA基因组的比例代表了健康和病理细胞结果之间的平衡。从机制上讲，心肌病会导致正常线粒体功能发生深刻改变。核线粒体基因组中的某些等位基因失衡与关键的线粒体能量蛋白有关。线粒体异质性可能在关键蛋白表达点表现出来，例如细胞色素c氧化酶（COX）。病理性mtDNA突变也与充血性心力衰竭的发生有关。有趣的是，不同异质群体的线粒体“正常与异常”比例可能在家族中出现。在人类健康与疾病的转化背景下，我们讨论了确定关键焦点以探究线粒体异质性在心肌病中的多种生物学作用的必要性。
