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酿酒酵母氧化损伤后线粒体和核基因组的完整性。

Mitochondrial and nuclear genomic integrity after oxidative damage in Saccharomyces cerevisiae.

机构信息

University of Alaska Anchorage, Alaska 99508, USA.

出版信息

Front Biosci (Landmark Ed). 2012 Jan 1;17(3):1079-93. doi: 10.2741/3974.

DOI:10.2741/3974
PMID:22201791
Abstract

All cells have the ability to adjust their metabolism to their changing environment to be able to survive. This adaptation is coordinated by various systems in the cell and mitochondria seem to play a unique and important role. Most endogenous oxidative damage to cells is actually generated as a byproduct of the mitochondrial function, which in turn damages mitochondrial structures more extensively due to their proximity to the source. Excessive damage to mitochondria leads to loss of parts or all of mtDNA, but unlike other organisms, S. cerevisiae cells are able to survive without mtDNA or respiration when grown on fermentative carbon sources. This allows studies of the role of mitochondria in the maintenance of cellular integrity, since lack of mitochondrial DNA frequently leads to genomic instability. Mitochondria are known for their role in respiration, ATP production and apoptosis, but it is now becoming clear that their function is intimately connected to diverse processes such as calcium and iron homeostasis and amino acid metabolism, and thus their dysfunction is not well tolerated. In this review, we discuss the mechanisms by which mitochondrial dysfunction can lead to genomic instability and the effect of the carbon source on this process.

摘要

所有细胞都有能力根据其变化的环境来调整其新陈代谢以生存。这种适应是由细胞内的各种系统协调的,而线粒体似乎起着独特而重要的作用。实际上,大多数细胞内的内源性氧化损伤是线粒体功能的副产物,由于它们靠近源头,线粒体结构因此受到更广泛的损伤。线粒体的过度损伤会导致 mtDNA 的部分或全部丢失,但与其他生物体不同的是,当在发酵碳源上生长时,酿酒酵母细胞即使没有 mtDNA 或呼吸作用也能存活。这使得研究线粒体在维持细胞完整性中的作用成为可能,因为缺乏线粒体 DNA 通常会导致基因组不稳定。线粒体以其在呼吸作用、ATP 产生和细胞凋亡中的作用而闻名,但现在越来越清楚的是,它们的功能与钙和铁平衡以及氨基酸代谢等多种过程密切相关,因此它们的功能障碍不能很好地耐受。在这篇综述中,我们讨论了线粒体功能障碍如何导致基因组不稳定以及碳源对这一过程的影响。

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