PQM-1 controls hypoxic survival via regulation of lipid metabolism.

TitlePQM-1 controls hypoxic survival via regulation of lipid metabolism.
Publication TypeJournal Article
Year of Publication2020
AuthorsHeimbucher, T, Hog, J, Gupta, P, Murphy, CT
JournalNat Commun
Volume11
Issue1
Pagination4627
Date Published2020 10 02
ISSN2041-1723
KeywordsAnimals, 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>

DOI10.1038/s41467-020-18369-w
Alternate JournalNat Commun
PubMed ID33009389
PubMed Central IDPMC7532158
Grant ListP50 GM071508 / GM / NIGMS NIH HHS / United States
R56 AG047344 / AG / NIA NIH HHS / United States