PQM-1 controls hypoxic survival via regulation of lipid metabolism

Nat Commun. 2020 Oct 2;11(1):4627. doi: 10.1038/s41467-020-18369-w.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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


  • Caenorhabditis elegans Proteins
  • Insulin
  • PQM-1 protein, C elegans
  • Trans-Activators
  • Vitellogenins
  • Glycogen