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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, Junbo Wu, Qian Bian, Yingchun Wang, Ye Tian
Science Advances
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.
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论文编号: |
DOI:10.1126/sciadv.abb2529 |
论文题目: |
NuRD Mediates Mitochondrial Stress–Induced Longevity via Chromatin Remodeling in Response to Acetyl-CoA Level |
英文论文题目: |
NuRD Mediates Mitochondrial Stress–Induced Longevity via Chromatin Remodeling in Response to Acetyl-CoA Level |
第一作者: |
Di Zhu, Xueying Wu, Jun Zhou, Xinyu Li, Xiahe Huang, Jiasheng Li, Junbo Wu, Qian Bian, Yingchun Wang, Ye Tian |
英文第一作者: |
Di Zhu, Xueying Wu, Jun Zhou, Xinyu Li, Xiahe Huang, Jiasheng Li, Junbo Wu, Qian Bian, Yingchun Wang, Ye Tian |
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2020-08-01 |
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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. |
英文摘要: |
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. |
刊物名称: |
Science Advances |
英文刊物名称: |
Science Advances |
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其它备注: |
Di Zhu, Xueying Wu, Jun Zhou, Xinyu Li, Xiahe Huang, Jiasheng Li, Junbo Wu, Qian Bian, Yingchun Wang, Ye Tian. NuRD Mediates Mitochondrial Stress–Induced Longevity via Chromatin Remodeling in Response to Acetyl-CoA Level. Science Advances. DOI:10.1126/sciadv.abb2529 |
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