| RRC ID |
65231
|
| Author |
Zhu D, Wu X, Zhou J, Li X, Huang X, Li J, Wu J, Bian Q, Wang Y, Tian Y.
|
| Title |
NuRD mediates mitochondrial stress-induced longevity via chromatin remodeling in response to acetyl-CoA level.
|
| Journal |
Sci Adv
|
| 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.
|
| Volume |
6(31)
|
| Pages |
eabb2529
|
| Published |
2020-7-1
|
| DOI |
10.1126/sciadv.abb2529
|
| PII |
abb2529
|
| PMID |
32789178
|
| PMC |
PMC7400466
|
| MeSH |
Acetyl Coenzyme A / metabolism
Acetylation
Animals
Caenorhabditis elegans / metabolism
Chromatin / metabolism
Chromatin Assembly and Disassembly*
Histones / metabolism
Longevity*
|
| Resource |
| C.elegans |
|
