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DAF-16 and TCER-1 Facilitate Adaptation to Germline Loss by Restoring Lipid Homeostasis and Repressing Reproductive Physiology in C. elegans

Amrit, FRG and Steenkiste, EM and Ratnappan, R and Chen, SW and McClendon, TB and Kostka, D and Yanowitz, J and Olsen, CP and Ghazi, A (2016) DAF-16 and TCER-1 Facilitate Adaptation to Germline Loss by Restoring Lipid Homeostasis and Repressing Reproductive Physiology in C. elegans. PLoS Genetics, 12 (2). ISSN 1553-7390

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Abstract

© 2016 Amrit et al. Elimination of the proliferating germline extends lifespan in C. elegans. This phenomenon provides a unique platform to understand how complex metazoans retain metabolic homeostasis when challenged with major physiological perturbations. Here, we demonstrate that two conserved transcription regulators essential for the longevity of germline-less adults, DAF-16/FOXO3A and TCER-1/TCERG1, concurrently enhance the expression of multiple genes involved in lipid synthesis and breakdown, and that both gene classes promote longevity. Lipidomic analyses revealed that key lipogenic processes, including de novo fatty acid synthesis, triglyceride production, desaturation and elongation, are augmented upon germline removal. Our data suggest that lipid anabolic and catabolic pathways are coordinately augmented in response to germline loss, and this metabolic shift helps preserve lipid homeostasis. DAF-16 and TCER-1 also perform essential inhibitory functions in germline-ablated animals. TCER-1 inhibits the somatic gene-expression program that facilitates reproduction and represses anti-longevity genes, whereas DAF-16 impedes ribosome biogenesis. Additionally, we discovered that TCER-1 is critical for optimal fertility in normal adults, suggesting that the protein acts as a switch supporting reproductive fitness or longevity depending on the presence or absence of the germline. Collectively, our data offer insights into how organisms adapt to changes in reproductive status, by utilizing the activating and repressive functions of transcription factors and coordinating fat production and degradation.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Amrit, FRG
Steenkiste, EM
Ratnappan, R
Chen, SW
McClendon, TBtbm13@pitt.eduTBM13
Kostka, Dkostka@pitt.eduKOSTKA
Yanowitz, J
Olsen, CP
Ghazi, Aghazia@pitt.eduGHAZIA
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorAshrafi, KavehUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Centers: Other Centers, Institutes, or Units > Magee-Women's Research Institute
Date: 1 February 2016
Date Type: Publication
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Journal or Publication Title: PLoS Genetics
Volume: 12
Number: 2
DOI or Unique Handle: 10.1371/journal.pgen.1005788
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Computational and Systems Biology
School of Medicine > Developmental Biology
School of Medicine > Obstetrics, Gynecology, and Reproductive Sciences
School of Medicine > Pediatrics
Refereed: Yes
ISSN: 1553-7390
Date Deposited: 23 Aug 2016 13:41
Last Modified: 12 Oct 2017 09:55
URI: http://d-scholarship.pitt.edu/id/eprint/28519

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