HIF-1 is required for heat acclimation in the nematode Caenorhabditis elegans

Millet Treinin, Judith Shliar, Huaqi Jiang, Jo Anne Powell-Coffman, Zohar Bromberg, Michal Horowitz

Research output: Contribution to journalArticle

79 Scopus citations


Chronic exposure to environmental-heat improves tolerance via heat acclimation (AC). Our previous data on mammals indicate that reprogramming the expression of genes coding for stress proteins and energy-metabolism enzymes plays a major role. Knowledge of pathways leading to AC is limited. For their identification, we established a Caenorhabditis elegans AC model and tested mutants in which signaling pathways pertinent to acclimatory responses are mutated. AC attained by maintaining adult C. elegans at 25°C for 18 h enhanced heat endurance of wild-type worms subjected to heat stress (35°C) and conferred protection against hypoxia and cadmium. Survival curves demonstrated that both daf-2 (insulin receptor pathway) showing enhanced heat tolerance and daf-16 loss-of-function (a transcription factor mediating DAF-2 signaling) mutants benefit from AC, suggesting that the insulin receptor pathway does not mediate AC. In contrast, the hif-1 (hypoxia inducible factor) loss-of-function strain did not show acclimation, and non-acclimated vhl-1 and egl-9 mutants (overexpressing HIF-1) had greater heat endurance than the wild type. Like mammals, HIF-1 and HSP72 levels increased in the wild-type AC nematodes. HSP72 upregulation in AC hif-1 mutants was also observed; however, it was insufficient to improve heat/stress tolerance, suggesting that HIF-1 upregulation is essential for acclimation, whereas HSP72 upregulation in the absence of HIF-1 is inadequate. We conclude that HIF-1 upregulation is both an evolutionarily conserved and a necessary component of heat acclimation. The known targets of HIF-1 imply that metabolic adaptations are essential for AC-dependent tolerance to heat and heavy metals, in addition to their known role in hypoxic adaptation.

Original languageEnglish (US)
Pages (from-to)17-24
Number of pages8
JournalPhysiological Genomics
StatePublished - Oct 2003



  • Cross-tolerance
  • HIF-1
  • HSP72
  • Heat acclimation

ASJC Scopus subject areas

  • Physiology
  • Genetics

Cite this

Treinin, M., Shliar, J., Jiang, H., Powell-Coffman, J. A., Bromberg, Z., & Horowitz, M. (2003). HIF-1 is required for heat acclimation in the nematode Caenorhabditis elegans. Physiological Genomics, 14, 17-24. https://doi.org/10.1152/physiolgenomics.00179.2002