Mitochondrial genome recovery by ATFS-1 is essential for development after starvation
Uma Naresh, Nandhitha ; Kim, Sookyung ; Shpilka, Tomer ; Yang, Qiyuan ; Du, Yunguang ; Haynes, Cole M
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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.
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Uma Naresh N, Kim S, Shpilka T, Yang Q, Du Y, Haynes CM. Mitochondrial genome recovery by ATFS-1 is essential for development after starvation. Cell Rep. 2022 Dec 27;41(13):111875. doi: 10.1016/j.celrep.2022.111875. PMID: 36577367; PMCID: PMC9922093.