NuRD mediates mitochondrial stress-induced longevity via chromatin remodeling in response to acetyl-CoA level

Mild mitochondrial stress experienced early in life can have beneficial effects on the life span of organisms through epigenetic regulations. Here, we report that acetyl-coenzyme A (CoA) represents a critical mitochondrial signal to regulate aging through the chromatin remodeling and histone deacety...

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Veröffentlicht in:Science advances 2020-07, Vol.6 (31), p.eabb2529-eabb2529
Hauptverfasser: Zhu, Di, Wu, Xueying, Zhou, Jun, Li, Xinyu, Huang, Xiahe, Li, Jiasheng, Wu, Junbo, Bian, Qian, Wang, Yingchun, Tian, Ye
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Sprache:eng
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Zusammenfassung:Mild mitochondrial stress experienced early in life can have beneficial effects on the life span of organisms through epigenetic regulations. Here, we report that acetyl-coenzyme A (CoA) represents a critical mitochondrial signal to regulate aging through the chromatin remodeling and histone deacetylase complex (NuRD) in . Upon mitochondrial stress, the impaired tricarboxylic acid cycle results in a decreased level of citrate, which accounts for reduced production of acetyl-CoA and consequently induces nuclear accumulation of the NuRD and a homeodomain-containing transcription factor DVE-1, thereby enabling decreased histone acetylation and chromatin reorganization. The metabolic stress response is thus established during early life and propagated into adulthood to allow transcriptional regulation for life-span extension. Furthermore, adding nutrients to restore acetyl-CoA production is sufficient to counteract the chromatin changes and diminish the longevity upon mitochondrial stress. Our findings uncover the molecular mechanism of the metabolite-mediated epigenome for the regulation of organismal aging.
ISSN:2375-2548
2375-2548
DOI:10.1126/sciadv.abb2529