RRC ID 53462
Author Amrit FR, Steenkiste EM, Ratnappan R, Chen SW, McClendon TB, Kostka D, Yanowitz J, Olsen CP, Ghazi A.
Title DAF-16 and TCER-1 Facilitate Adaptation to Germline Loss by Restoring Lipid Homeostasis and Repressing Reproductive Physiology in C. elegans.
Journal PLoS Genet
Abstract 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.
Volume 12(2)
Pages e1005788
Published 2016-2-1
DOI 10.1371/journal.pgen.1005788
PMID 26862916
PMC PMC4749232
MeSH Adaptation, Physiological* Animals Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / metabolism* Diet Down-Regulation / genetics Fatty Acids / metabolism Fertility / genetics Forkhead Transcription Factors / metabolism* Gene Expression Regulation, Developmental Germ Cells / metabolism* Homeostasis* Lipid Metabolism* Longevity Mutation / genetics Peptide Elongation Factors / metabolism* Protein Biosynthesis / genetics Receptors, Notch / metabolism Reproduction Transcriptome / genetics Triglycerides / metabolism Up-Regulation / genetics
IF 5.175
Times Cited 27
C.elegans tm1452