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

ABSTRACT: 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 Caenorhabditis elegans. 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.

SUBMITTER: Zhu D

PROVIDER: S-EPMC7400466 | biostudies-literature |

REPOSITORIES: biostudies-literature

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The nucleosome remodeling and deacetylase (NuRD) complex mediates the mitochondrial unfolded protein response and longevity in C. elegans

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