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Mitochondrial DNA: cellular genotoxic stress sentinel
Trends in Biochemical Sciences ( IF 11.6 ) Pub Date : 2021-06-01 , DOI: 10.1016/j.tibs.2021.05.004
Zheng Wu 1 , Alva G Sainz 2 , Gerald S Shadel 3
Affiliation  

High copy number, damage prone, and lean on repair mechanisms are unique features of mitochondrial DNA (mtDNA) that are hard to reconcile with its essentiality for oxidative phosphorylation, the primary function ascribed to this maternally inherited component of our genome. We propose that mtDNA is also a genotoxic stress sentinel, as well as a direct second messenger of this type of cellular stress. Here, we discuss existing evidence for this sentinel/effector role through the ability of mtDNA to escape the confines of the mitochondrial matrix and activate nuclear DNA damage/repair responses via interferon-stimulated gene products and other downstream effectors. However, this arrangement may come at a cost, leading to cancer chemoresistance and contributing to inflammation, disease pathology, and aging.



中文翻译:

线粒体 DNA:细胞遗传毒性应激哨兵

高拷贝数、易损伤和依赖修复机制是线粒体 DNA (mtDNA) 的独特特征,很难与其对氧化磷酸化的重要性相协调,氧化磷酸化是我们基因组中这一母系遗传成分的主要功能。我们提出 mtDNA 也是一种遗传毒性应激哨兵,也是此类细胞应激的直接第二信使。在这里,我们通过 mtDNA 逃脱线粒体基质的限制并通过干扰素刺激的基因产物和其他下游效应子激活核 DNA 损伤/修复反应的能力,讨论了这种哨兵/效应子作用的现有证据。然而,这种安排可能是有代价的,导致癌症化疗耐药并导致炎症、疾病病理学和衰老。

更新日期:2021-06-01
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