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bioRxiv · 10.1101/2022.05.19.492689

Mitochondrial genome recovery by ATFS-1 is essential for development following starvation

Naresh, N. U.·Shpilka, T.·Yang, Q.·Du, Y.·Haynes, C.
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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) number and leads to aging-related phenotypes. Here, we demonstrate that the bZIP protein ATFS-1, a mediator of the mitochondrial unfolded protein response (UPRmt), is required to promote growth and establish a functional germline following prolonged starvation. Surprisingly, we found that the recovery of mtDNA copy number and development following starvation required mitochondrial-localized ATFS-1 but not its nuclear transcription activity. Lastly, we found that the insulin-like receptor DAF-2, functions upstream of ATFS-1 to modulate mtDNA content. We demonstrate that reducing DAF-2 activity represses ATFS-1 nuclear function while causing an increase in mtDNA content partly mediated by mitochondrial-localized ATFS-1. Combined, our data indicate the importance of the UPRmt in recovering mitochondrial mass and suggests that atfs-1-dependent mtDNA replication precedes mitochondrial network expansion following starvation.

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Naresh, N. U., Shpilka, T., Yang, Q., Du, Y., Haynes, C.. 2022-05-19. Mitochondrial genome recovery by ATFS-1 is essential for development following starvation. https://doi.org/10.1101/2022.05.19.492689

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