生物
蛋白质稳态
线粒体
氧化磷酸化
细胞生物学
转录因子
伴侣(临床)
遗传学
生物化学
基因
医学
病理
作者
Amrita M. Nargund,Christopher J. Fiorese,Mark W. Pellegrino,Peng Deng,Cole M. Haynes
出处
期刊:Molecular Cell
[Elsevier]
日期:2015-04-01
卷期号:58 (1): 123-133
被引量:354
标识
DOI:10.1016/j.molcel.2015.02.008
摘要
Mitochondrial diseases and aging are associated with defects in the oxidative phosphorylation machinery (OXPHOS), which are the only complexes composed of proteins encoded by separate genomes. To better understand genome coordination and OXPHOS recovery during mitochondrial dysfunction, we examined ATFS-1, a transcription factor that regulates mitochondria-to-nuclear communication during the mitochondrial UPR, via ChIP-sequencing. Surprisingly, in addition to regulating mitochondrial chaperone, OXPHOS complex assembly factor, and glycolysis genes, ATFS-1 bound directly to OXPHOS gene promoters in both the nuclear and mitochondrial genomes. Interestingly, atfs-1 was required to limit the accumulation of OXPHOS transcripts during mitochondrial stress, which required accumulation of ATFS-1 in the nucleus and mitochondria. Because balanced ATFS-1 accumulation promoted OXPHOS complex assembly and function, our data suggest that ATFS-1 stimulates respiratory recovery by fine-tuning OXPHOS expression to match the capacity of the suboptimal protein-folding environment in stressed mitochondria, while simultaneously increasing proteostasis capacity.
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