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

Autor:	Gerisch B; Department of Molecular Genetics of Ageing, Max Planck Institute for Biology of Ageing, Cologne 50931, Germany., Tharyan RG; Department of Molecular Genetics of Ageing, Max Planck Institute for Biology of Ageing, Cologne 50931, Germany., Mak J; Department of Molecular Genetics of Ageing, Max Planck Institute for Biology of Ageing, Cologne 50931, Germany., Denzel SI; Department of Molecular Genetics of Ageing, Max Planck Institute for Biology of Ageing, Cologne 50931, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, University of Cologne, Cologne 50931, Germany., Popkes-van Oepen T; Department of Molecular Genetics of Ageing, Max Planck Institute for Biology of Ageing, Cologne 50931, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, University of Cologne, Cologne 50931, Germany., Henn N; Department of Molecular Genetics of Ageing, Max Planck Institute for Biology of Ageing, Cologne 50931, Germany., Antebi A; Department of Molecular Genetics of Ageing, Max Planck Institute for Biology of Ageing, Cologne 50931, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, University of Cologne, Cologne 50931, Germany. Electronic address: aantebi@age.mpg.de.
Jazyk:	angličtina
Zdroj:	Developmental cell [Dev Cell] 2020 May 04; Vol. 53 (3), pp. 316-329.e5. Date of Electronic Publication: 2020 Apr 16.
DOI:	10.1016/j.devcel.2020.03.014
Abstrakt:	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. Competing Interests: Declaration of Interests The authors declare no competing interests. (Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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