RRC ID 76314
著者 Uma Naresh N, Kim S, Shpilka T, Yang Q, Du Y, Haynes CM.
タイトル Mitochondrial genome recovery by ATFS-1 is essential for development after starvation.
ジャーナル Cell Rep
Abstract Nutrient availability regulates the C. elegans life cycle as well as mitochondrial physiology. Food deprivation significantly reduces mitochondrial genome (mtDNA) numbers and leads to aging-related phenotypes. Here we show that the bZIP (basic leucine zipper) protein ATFS-1, a mediator of the mitochondrial unfolded protein response (UPRmt), is required to promote growth and establish a functional germline after prolonged starvation. We find that recovery of mtDNA copy numbers and development after starvation requires mitochondrion-localized ATFS-1 but not its nuclear transcription activity. We also find that the insulin-like receptor DAF-2 functions upstream of ATFS-1 to modulate mtDNA content. We show that reducing DAF-2 activity represses ATFS-1 nuclear function while causing an increase in mtDNA content, partly mediated by mitochondrion-localized ATFS-1. Our data indicate the importance of the UPRmt in recovering mitochondrial mass and suggest that atfs-1-dependent mtDNA replication precedes mitochondrial network expansion after starvation.
巻・号 41(13)
ページ 111875
公開日 2022-12-27
DOI 10.1016/j.celrep.2022.111875
PII S2211-1247(22)01771-5
PMID 36577367
PMC PMC9922093
MeSH Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism DNA, Mitochondrial / genetics DNA, Mitochondrial / metabolism Genome, Mitochondrial* Mitochondria / genetics Mitochondria / metabolism Unfolded Protein Response
リソース情報
線虫 tm598