RRC ID 65296
Author Heimbucher T, Hog J, Gupta P, Murphy CT.
Title PQM-1 controls hypoxic survival via regulation of lipid metabolism.
Journal Nat Commun
Abstract Animals have evolved responses to low oxygen conditions to ensure their survival. Here, we have identified the C. elegans zinc finger transcription factor PQM-1 as a regulator of the hypoxic stress response. PQM-1 is required for the longevity of insulin signaling mutants, but surprisingly, loss of PQM-1 increases survival under hypoxic conditions. PQM-1 functions as a metabolic regulator by controlling oxygen consumption rates, suppressing hypoxic glycogen levels, and inhibiting the expression of the sorbitol dehydrogenase-1 SODH-1, a crucial sugar metabolism enzyme. PQM-1 promotes hypoxic fat metabolism by maintaining the expression of the stearoyl-CoA desaturase FAT-7, an oxygen consuming, rate-limiting enzyme in fatty acid biosynthesis. PQM-1 activity positively regulates fat transport to developing oocytes through vitellogenins under hypoxic conditions, thereby increasing survival rates of arrested progeny during hypoxia. Thus, while pqm-1 mutants increase survival of mothers, ultimately this loss is detrimental to progeny survival. Our data support a model in which PQM-1 controls a trade-off between lipid metabolic activity in the mother and her progeny to promote the survival of the species under hypoxic conditions.
Volume 11(1)
Pages 4627
Published 2020-10-2
DOI 10.1038/s41467-020-18369-w
PII 10.1038/s41467-020-18369-w
PMID 33009389
PMC PMC7532158
MeSH Animals Caenorhabditis elegans / embryology Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Embryo, Mammalian / metabolism Gene Expression Regulation Glycogen / metabolism Hypoxia / metabolism* Insulin / metabolism Larva / metabolism Lipid Metabolism* Mutation / genetics Oxygen Consumption Signal Transduction Stress, Physiological Survival Analysis Trans-Activators / genetics Trans-Activators / metabolism* Transcription, Genetic Vitellogenins / metabolism
Resource
C.elegans tm4063