Title | PQM-1 controls hypoxic survival via regulation of lipid metabolism. |
Publication Type | Journal Article |
Year of Publication | 2020 |
Authors | Heimbucher, T, Hog, J, Gupta, P, Murphy, CT |
Journal | Nat Commun |
Volume | 11 |
Issue | 1 |
Pagination | 4627 |
Date Published | 2020 10 02 |
ISSN | 2041-1723 |
Keywords | Animals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Embryo, Mammalian, Gene Expression Regulation, Glycogen, Hypoxia, Insulin, Larva, Lipid Metabolism, Mutation, Oxygen Consumption, Signal Transduction, Stress, Physiological, Survival Analysis, Trans-Activators, Transcription, Genetic, Vitellogenins |
Abstract | <p>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.</p> |
DOI | 10.1038/s41467-020-18369-w |
Alternate Journal | Nat Commun |
PubMed ID | 33009389 |
PubMed Central ID | PMC7532158 |
Grant List | P50 GM071508 / GM / NIGMS NIH HHS / United States R56 AG047344 / AG / NIA NIH HHS / United States |