| RRC ID |
76314
|
| Author |
Uma Naresh N, Kim S, Shpilka T, Yang Q, Du Y, Haynes CM.
|
| Title |
Mitochondrial genome recovery by ATFS-1 is essential for development after starvation.
|
| Journal |
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.
|
| Volume |
41(13)
|
| Pages |
111875
|
| Published |
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
|
| Resource |
| C.elegans |
tm598 |
