Mitochondrial Control of Genomic Instability in Cancer.
Mitochondrial Control of Genomic Instability in Cancer.
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癌症中基因组不稳定性的线粒体控制
DOI：
10.3390/cancers13081914
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发表时间：
2021-04-15
期刊：
影响因子：
5.2
通讯作者：
Giorgi C
中科院分区：
文献类型：
--
作者：
Bonora M;Missiroli S;Perrone M;Fiorica F;Pinton P;Giorgi C
癌细胞在其标志性特征中表现出基因组不稳定性。这是一种积累基因组改变的渐进趋势，这种改变导致调控细胞分裂和肿瘤抑制的基因受损。基因组不稳定性有利于促进生存的突变出现，增加了这些突变传递给子细胞的可能性，并对癌症进展产生重大影响。在影响这一现象的众多因素中，线粒体生理学逐渐凸显出来。线粒体通过对DNA改变作出反应以触发细胞死亡程序以及作为DNA损伤的一个来源，与基因组不稳定性相关联。癌症中典型的线粒体改变会使线粒体细胞死亡途径脱敏，促进获得新突变的细胞存活，或者会刺激线粒体介导的DNA损伤，提高突变率和基因组不稳定性本身。
众所周知，线粒体参与肿瘤形成和进展的多个方面。它们确实能够改变细胞参与调节性细胞死亡的敏感性，调节促生存信号转导通路，并赋予适应特定肿瘤细胞需求的代谢可塑性。有趣的是，在肿瘤疾病中线粒体一个相对探索较少的方面是它们对作为疾病演变基础的特征性基因组不稳定性的贡献。在这篇综述中，我们总结了癌症中线粒体改变耐受和支持导致基因组不稳定性的DNA突变积累的已知机制。我们描述了近期阐明线粒体对DNA损伤的反应以及线粒体对促进DNA改变积累的直接贡献的研究。
Cancer cells display among its hallmark genomic instability. This is a progressive tendency in accumulate genome alteration which contributes to the damage of genes regulating cell division and tumor suppression. Genomic instability favors the appearance of survival-promoting mutations, increasing the likelihood that those mutations will propagate into daughter cells and have a significant impact on cancer progression. Among the many factor influencing this phenomenon, mitochondrial physiology is emerging. Mitochondria are bound to genomic instability by responding to DNA alteration to trigger cell death programs and as a source for DNA damage. Mitochondrial alterations prototypical of cancer can desensitize the mitochondrial route of cell death, facilitating the survival of cell acquiring new mutations, or can stimulate mitochondrial mediated DNA damage, boosting the mutation rate and genomic instability itself. Mitochondria are well known to participate in multiple aspects of tumor formation and progression. They indeed can alter the susceptibility of cells to engage regulated cell death, regulate pro-survival signal transduction pathways and confer metabolic plasticity that adapts to specific tumor cell demands. Interestingly, a relatively poorly explored aspect of mitochondria in neoplastic disease is their contribution to the characteristic genomic instability that underlies the evolution of the disease. In this review, we summarize the known mechanisms by which mitochondrial alterations in cancer tolerate and support the accumulation of DNA mutations which leads to genomic instability. We describe recent studies elucidating mitochondrial responses to DNA damage as well as the direct contribution of mitochondria to favor the accumulation of DNA alterations.
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影响因子：
5.9
作者：
Anso E;Mullen AR;Felsher DW;Matés JM;Deberardinis RJ;Chandel NS
通讯作者：
Chandel NS
影响因子：
6.4
作者：
Daskalos, Alexandros;Nikolaidis, Georgios;Liloglou, Triantafillos
通讯作者：
Liloglou, Triantafillos
影响因子：
13.3
作者：
Chao, Tung;Shih, Hsueh-Tzu;Chang, Zee-Fen
通讯作者：
Chang, Zee-Fen
影响因子：
8.8
作者：
BHATHAL, PS;BROWN, RW;RUSSELL, IS
通讯作者：
RUSSELL, IS
DOI：
10.1007/978-981-15-0602-4_9
发表时间：
2019-01-01
期刊：
AUTOPHAGY: BIOLOGY AND DISEASES: BASIC SCIENCE
影响因子：
--
作者：
Gao, Qi
通讯作者：
Gao, Qi