DELETERIOUS MITOCHONDRIAL-DNA MUTATIONS ACCUMULATE IN AGING HUMAN TISSUES
DELETERIOUS MITOCHONDRIAL-DNA MUTATIONS ACCUMULATE IN AGING HUMAN TISSUES
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DOI：
10.1016/0921-8734(92)90020-p
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发表时间：
1992-09-01
期刊：
影响因子：
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通讯作者：
CORTOPASSI, G
中科院分区：
文献类型：
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作者：
ARNHEIM, N;CORTOPASSI, G
本文综述了线粒体DNA （mtDNA）突变对衰老表型的贡献的知识现状。它的主要重点是发现mtDNA的缺失，这种缺失以前被认为只发生在神经肌肉疾病患者身上。一种特殊的缺失（mtDNA4977）主要在正常人的肌肉和大脑等非分裂细胞中随着年龄的增长而积累。随着年龄的增长，心脏和大脑的缺失水平增加了1000多倍，其他组织的缺失程度较低。在大脑中，不同的区域有不同程度的缺失。组织中缺失的高水平积累与高耗氧量有关。我们推测mtDNA的氧化损伤可能是“灾难性的”；影响参与电子传递的线粒体编码多肽的突变可能增加自由基的产生，导致更多的mtDNA损伤。
This paper reviews the current state of knowledge of the contribution of mitochondrial DNA (mtDNA) mutations to the phenotype of aging. Its major focus is on the discovery of deletions of mtDNA which previously were thought to occur only in individuals with neuromuscular disease. One particular deletion (mtDNA4977) accumulates with age primarily in non-dividing cells such as muscle and brain of normal individuals. The level of the deletion rises with age by more than 1000 fold in heart and brain and to a lesser extent in other tissues. In the brain, different regions have substantially different levels of the deletion. High levels of accumulation of the deletion in tissues are correlated with high oxygen consumption. We speculate that oxidative damage to mtDNA may be 'catastrophic'; mutations affecting mitochondrially encoded polypeptides involved in electron transport could increase free radical generation leading to more mtDNA damage.