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线粒体DNA修复与衰老

Mitochondrial DNA repair and aging.

作者信息

Mandavilli Bhaskar S, Santos Janine H, Van Houten Bennett

机构信息

Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, 111 Alexander Drive, P.O. Box 12233, Research Triangle Park, NC 27709, USA.

出版信息

Mutat Res. 2002 Nov 30;509(1-2):127-51. doi: 10.1016/s0027-5107(02)00220-8.

Abstract

The mitochondrial electron transport chain plays an important role in energy production in aerobic organisms and is also a significant source of reactive oxygen species that damage DNA, RNA and proteins in the cell. Oxidative damage to the mitochondrial DNA is implicated in various degenerative diseases, cancer and aging. The importance of mitochondrial ROS in age-related degenerative diseases is further strengthened by studies using animal models, Caenorhabditis elegans, Drosophila and yeast. Research in the last several years shows that mitochondrial DNA is more susceptible to various carcinogens and ROS when compared to nuclear DNA. DNA damage in mammalian mitochondria is repaired by base excision repair (BER). Studies have shown that mitochondria contain all the enzymes required for BER. Mitochondrial DNA damage, if not repaired, leads to disruption of electron transport chain and production of more ROS. This vicious cycle of ROS production and mtDNA damage ultimately leads to energy depletion in the cell and apoptosis.

摘要

线粒体电子传递链在需氧生物的能量产生中起着重要作用,也是活性氧的重要来源,这些活性氧会损害细胞中的DNA、RNA和蛋白质。线粒体DNA的氧化损伤与各种退行性疾病、癌症和衰老有关。使用动物模型、秀丽隐杆线虫、果蝇和酵母进行的研究进一步强化了线粒体活性氧在与年龄相关的退行性疾病中的重要性。过去几年的研究表明,与核DNA相比,线粒体DNA更容易受到各种致癌物和活性氧的影响。哺乳动物线粒体中的DNA损伤通过碱基切除修复(BER)来修复。研究表明,线粒体含有BER所需的所有酶。线粒体DNA损伤若不修复,会导致电子传递链中断并产生更多的活性氧。这种活性氧产生和线粒体DNA损伤的恶性循环最终导致细胞能量耗竭和凋亡。

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