HLH-30/TFEB Is a Master Regulator of Reproductive Quiescence.

Birgit Gerisch, Rebecca George Tharyan, Jennifer Mak, Sarah I Denzel, Till Popkes-van Oepen, Nadine Henn, Adam Antebi

Developmental cell 2020 May 04

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All animals have evolved the ability to survive nutrient deprivation, and nutrient signaling pathways are conserved modulators of health and disease. In C. elegans, late-larval starvation provokes the adult reproductive diapause (ARD), a long-lived quiescent state that enables survival for months without food, yet underlying molecular mechanisms remain unknown. Here, we show that ARD is distinct from other forms of diapause, showing little requirement for canonical longevity pathways, autophagy, and fat metabolism. Instead it requires the HLH-30/TFEB transcription factor to promote the morphological and physiological remodeling involved in ARD entry, survival, and recovery, suggesting that HLH-30 is a master regulator of reproductive quiescence. HLH-30 transcriptome and genetic analyses reveal that Max-like HLH factors, AMP-kinase, mTOR, protein synthesis, and mitochondrial fusion are target processes that promote ARD longevity. ARD thus rewires metabolism to ensure long-term survival and may illuminate similar mechanisms acting in stem cell quiescence and long-term fasting. Copyright © 2020 Elsevier Inc. All rights reserved.

Citation

Birgit Gerisch, Rebecca George Tharyan, Jennifer Mak, Sarah I Denzel, Till Popkes-van Oepen, Nadine Henn, Adam Antebi. HLH-30/TFEB Is a Master Regulator of Reproductive Quiescence. Developmental cell. 2020 May 04;53(3):316-329.e5