NuRD mediates mitochondrial stress–induced longevity via chromatin remodeling in response to acetyl-CoA level
Di Zhu, Xueying Wu, Jun Zhou, Xinyu Li, Xiahe Huang, Jiasheng Li, Jun-Bo Wu, Qian Bian, Yingchun Wang, Ye Tian
Abstract
. 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.