The transcriptional coactivator CBP/p300 is an evolutionarily conserved node that promotes longevity in response to mitochondrial stress.

ABSTRACT: Organisms respond to mitochondrial stress by activating multiple defense pathways including the mitochondrial unfolded protein response (UPR^mt). However, how UPR^mt regulators are orchestrated to transcriptionally activate stress responses remains largely unknown. Here we identified CBP-1, the worm ortholog of the mammalian acetyltransferases CBP/p300, as an essential regulator of the UPR^mt, as well as mitochondrial stress-induced immune response, reduction of amyloid-β aggregation and lifespan extension in Caenorhabditis elegans. Mechanistically, CBP-1 acts downstream of histone demethylases, JMJD-1.2/JMJD-3.1, and upstream of UPR^mt transcription factors including ATFS-1, to systematically induce a broad spectrum of UPR^mt genes

SUBMITTER: Li TY 

PROVIDER: S-EPMC7116894 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature