脂质过氧化和mtDNA变性。一个假设

Andrew M. Hruszkewycz
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引用次数: 66

摘要

脂质过氧化的最终产物在体细胞的生命中积累。据推测,脂质过氧化的遗传毒性中间体可能在引起与年龄相关的DNA突变中起作用。这种突变很可能发生在线粒体基因组中,因为与核DNA不同,线粒体基因组不受组蛋白和修复系统的保护。此外,它位于线粒体膜附近,线粒体电子传递系统产生的自由基可引发脂质过氧化。这一观点得到了体外实验的支持,该实验表明,当线粒体经历脂质过氧化时,线粒体DNA会受损。
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Lipid peroxidation and mtDNA degeneration. A hypothesis

End-products of lipid peroxidation accumulate during the life of somatic cells. It is hypothesized that genotoxic intermediates of lipid peroxidation may have a role in causing age-associated DNA mutations. Such mutations are likely to accrue in the mitochondrial genome because it, unlike nuclear DNA, is not protected by histones and repair systems. In addition, it is located near the mitochondrial membrane where lipid peroxidation can be initiated by free radicals produced by the mitochondrial electron transport system. This idea is supported by in vitro experiments which show that mitochondrial DNA is damaged when mitochondria undergo lipid peroxidation.

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Publisher's note Editorial An accessory protein enhances both DNA binding and activity of DNA polymerase α isolated from normal, but not transformed, human fibroblasts Differences in the spectrum of spontaneous mutations in the hprt gene between tumor cells of the microsatellite mutator phenotype Spermatid micronucleus analysis of aging effects in hamsters
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