Gene Symbol: hif-1
Description: HIF (Hypoxia Inducible Factor) homologa;Hypoxia-inducible factor 1
Alias: HIF (Hypoxia Inducible Factor) homologa;Hypoxia-inducible factor 1
Species: Caenorhabditis elegans

Top Publications

  1. Epstein A, Gleadle J, McNeill L, Hewitson K, O ROURKE J, Mole D, et al. C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation. Cell. 2001;107:43-54 pubmed
  2. Lee S, Hwang A, Kenyon C. Inhibition of respiration extends C. elegans life span via reactive oxygen species that increase HIF-1 activity. Curr Biol. 2010;20:2131-6 pubmed publisher
    ..In this way, HIF-1 appears to link respiratory stress in the mitochondria to a nuclear transcriptional response that promotes longevity. ..
  3. Shao Z, Zhang Y, Ye Q, Saldanha J, Powell Coffman J. C. elegans SWAN-1 Binds to EGL-9 and regulates HIF-1-mediated resistance to the bacterial pathogen Pseudomonas aeruginosa PAO1. PLoS Pathog. 2010;6:e1001075 pubmed publisher
    ..aeruginosa. These data support a model in which SWAN-1, MBK-1 and EGL-9 regulate HIF-1 transcriptional activity and modulate resistance to P. aeruginosa PAO1 fast killing. ..
  4. Sendoel A, Kohler I, Fellmann C, Lowe S, Hengartner M. HIF-1 antagonizes p53-mediated apoptosis through a secreted neuronal tyrosinase. Nature. 2010;465:577-83 pubmed publisher
    ..Our findings identify a novel link between hypoxia and programmed cell death, and provide a paradigm for HIF-1 dictating apoptotic cell fate at a distance. ..
  5. Chen D, Thomas E, Kapahi P. HIF-1 modulates dietary restriction-mediated lifespan extension via IRE-1 in Caenorhabditis elegans. PLoS Genet. 2009;5:e1000486 pubmed publisher
    ..Therefore, our results demonstrate a tissue-specific role for HIF-1 in the lifespan extension by DR involving the IRE-1 ER stress pathway. ..
  6. Pocock R, Hobert O. Oxygen levels affect axon guidance and neuronal migration in Caenorhabditis elegans. Nat Neurosci. 2008;11:894-900 pubmed publisher
    ..Similar genetic pathways may cause aberrant human brain development under hypoxic conditions. ..
  7. Shen C, Nettleton D, Jiang M, Kim S, Powell Coffman J. Roles of the HIF-1 hypoxia-inducible factor during hypoxia response in Caenorhabditis elegans. J Biol Chem. 2005;280:20580-8 pubmed
    ..The microarray data presented herein also provide clear evidence for an HIF-1-independent pathway for hypoxia response, and this pathway regulates the expression of multiple heat shock proteins and several transcription factors. ..
  8. Padilla P, Nystul T, Zager R, Johnson A, Roth M. Dephosphorylation of cell cycle-regulated proteins correlates with anoxia-induced suspended animation in Caenorhabditis elegans. Mol Biol Cell. 2002;13:1473-83 pubmed
    ..Thus, dephosphorylation of specific proteins correlate with the establishment and/or maintenance of a state of anoxia-induced suspended animation. ..
  9. Romney S, Newman B, Thacker C, Leibold E. HIF-1 regulates iron homeostasis in Caenorhabditis elegans by activation and inhibition of genes involved in iron uptake and storage. PLoS Genet. 2011;7:e1002394 pubmed publisher
    ..These data show that HIF-1 regulates intestinal iron homeostasis during iron deficiency by activating and inhibiting genes involved in iron uptake and storage. ..

More Information


  1. Mehta R, Steinkraus K, Sutphin G, Ramos F, Shamieh L, Huh A, et al. Proteasomal regulation of the hypoxic response modulates aging in C. elegans. Science. 2009;324:1196-8 pubmed publisher
    ..VHL-1 and HIF-1 control longevity by a mechanism distinct from both dietary restriction and insulin-like signaling. These findings define VHL-1 and the hypoxic response as an alternative longevity and protein homeostasis pathway. ..
  2. Zhang Y, Shao Z, Zhai Z, Shen C, Powell Coffman J. The HIF-1 hypoxia-inducible factor modulates lifespan in C. elegans. PLoS ONE. 2009;4:e6348 pubmed publisher
    ..These data establish HIF-1 as one of the key stress-responsive transcription factors that modulate longevity in C. elegans and advance our understanding of the regulatory networks that link oxygen homeostasis and aging. ..
  3. Treinin M, Shliar J, Jiang H, Powell Coffman J, Bromberg Z, Horowitz M. HIF-1 is required for heat acclimation in the nematode Caenorhabditis elegans. Physiol Genomics. 2003;14:17-24 pubmed
    ..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. ..
  4. Leiser S, Begun A, Kaeberlein M. HIF-1 modulates longevity and healthspan in a temperature-dependent manner. Aging Cell. 2011;10:318-26 pubmed publisher
    ..Knockdown of hif-1 results in nuclear relocalization of the FOXO transcription factor DAF-16, and DAF-16 is required for life span extension from deletion of hif-1 at all temperatures regardless of censoring. ..
  5. Shen C, Shao Z, Powell Coffman J. The Caenorhabditis elegans rhy-1 gene inhibits HIF-1 hypoxia-inducible factor activity in a negative feedback loop that does not include vhl-1. Genetics. 2006;174:1205-14 pubmed
    ..Collectively, these data support models in which RHY-1 and EGL-9 function in VHL-1-independent pathway(s) to repress HIF-1 transcriptional activity. ..
  6. Shao Z, Zhang Y, Powell Coffman J. Two distinct roles for EGL-9 in the regulation of HIF-1-mediated gene expression in Caenorhabditis elegans. Genetics. 2009;183:821-9 pubmed publisher
  7. Jiang H, Guo R, Powell Coffman J. The Caenorhabditis elegans hif-1 gene encodes a bHLH-PAS protein that is required for adaptation to hypoxia. Proc Natl Acad Sci U S A. 2001;98:7916-21 pubmed
    ..Additionally, we find that nuclear localization of AHA-1 is disrupted in an hif-1 mutant. This finding suggests that heterodimerization may be a prerequisite for efficient nuclear translocation of AHA-1. ..
  8. Budde M, Roth M. Hydrogen sulfide increases hypoxia-inducible factor-1 activity independently of von Hippel-Lindau tumor suppressor-1 in C. elegans. Mol Biol Cell. 2010;21:212-7 pubmed publisher
    ..Because H(2)S is naturally produced by animal cells, our results suggest that endogenous H(2)S may influence HIF-1 activity. ..
  9. Grove C, De Masi F, Barrasa M, Newburger D, Alkema M, Bulyk M, et al. A multiparameter network reveals extensive divergence between C. elegans bHLH transcription factors. Cell. 2009;138:314-27 pubmed publisher
    ..For a video summary of this article, see the PaperFlick file available with the online Supplemental Data. ..
  10. Livshits L, Chatterjee A, Karbian N, Abergel R, Abergel Z, Gross E. Mechanisms of defense against products of cysteine catabolism in the nematode Caenorhabditis elegans. Free Radic Biol Med. 2017;104:346-359 pubmed publisher
    ..Finally, we show that sulfide resistance varies among wild C. elegans and other nematode species, suggesting that tolerance to sulfide was naturally selected in certain habitats. ..
  11. Kamal M, D Amora D, Kubiseski T. Loss of hif-1 promotes resistance to the exogenous mitochondrial stressor ethidium bromide in Caenorhabditis elegans. BMC Cell Biol. 2016;17 Suppl 1:34 pubmed publisher
    ..We propose that EtBr-induced HIF-1 activates pathways that are antagonistic in conferring protection against EtBr toxicity and that blocking HIF-1 activity may promote survival in cells with compromised mitochondrial function. ..
  12. Gharbi H, Fabretti F, Bharill P, Rinschen M, Brinkkötter S, Frommolt P, et al. Loss of the Birt-Hogg-Dubé gene product folliculin induces longevity in a hypoxia-inducible factor-dependent manner. Aging Cell. 2013;12:593-603 pubmed publisher
    ..These findings define FLCN as a player in HIF-dependent longevity signaling and connect organismal aging, stress resistance, and regulation of longevity with the formation of renal cell carcinoma. ..
  13. Leiser S, Fletcher M, Begun A, Kaeberlein M. Life-span extension from hypoxia in Caenorhabditis elegans requires both HIF-1 and DAF-16 and is antagonized by SKN-1. J Gerontol A Biol Sci Med Sci. 2013;68:1135-44 pubmed publisher
    ..Collectively, our results show that hypoxia modulates longevity in a complex manner, likely involving components in addition to HIF-1. ..
  14. Miller D, Roth M. C. elegans are protected from lethal hypoxia by an embryonic diapause. Curr Biol. 2009;19:1233-7 pubmed publisher
    ..This response is likely to be an important strategy to improve offspring survival in harsh conditions and allow adults to find environments more suitable for reproductive success. ..
  15. Xie M, Roy R. Increased levels of hydrogen peroxide induce a HIF-1-dependent modification of lipid metabolism in AMPK compromised C. elegans dauer larvae. Cell Metab. 2012;16:322-35 pubmed publisher
  16. Maisel M, Habisch H, Royer L, Herr A, Milosevic J, Hermann A, et al. Genome-wide expression profiling and functional network analysis upon neuroectodermal conversion of human mesenchymal stem cells suggest HIF-1 and miR-124a as important regulators. Exp Cell Res. 2010;316:2760-78 pubmed publisher
  17. Mendenhall A, LeBlanc M, Mohan D, Padilla P. Reduction in ovulation or male sex phenotype increases long-term anoxia survival in a daf-16-independent manner in Caenorhabditis elegans. Physiol Genomics. 2009;36:167-78 pubmed publisher
  18. Leiser S, Miller H, Rossner R, Fletcher M, Leonard A, Primitivo M, et al. Cell nonautonomous activation of flavin-containing monooxygenase promotes longevity and health span. Science. 2015;350:1375-1378 pubmed publisher
    ..FMOs are conserved in eukaryotes and induced by multiple life span-extending interventions in mice, which suggests that these enzymes may play a critical role in promoting health and longevity across phyla. ..
  19. Alam T, Maruyama H, Li C, Pastuhov S, Nix P, Bastiani M, et al. Axotomy-induced HIF-serotonin signalling axis promotes axon regeneration in C. elegans. Nat Commun. 2016;7:10388 pubmed publisher
    ..SER-7 also promotes axon regeneration by activating the cyclic AMP (cAMP) signalling pathway. Thus, HIF-1-mediated activation of 5-HT signalling promotes axon regeneration by activating both the RhoA and cAMP pathways. ..
  20. Ma D, Vozdek R, Bhatla N, Horvitz H. CYSL-1 interacts with the O2-sensing hydroxylase EGL-9 to promote H2S-modulated hypoxia-induced behavioral plasticity in C. elegans. Neuron. 2012;73:925-40 pubmed publisher
    ..These findings demonstrate that CYSL-1 acts to transduce signals from H(2)S to EGL-9 to regulate O(2)-dependent behavioral plasticity in C. elegans. ..
  21. Hwang A, Ryu E, Artan M, Chang H, Kabir M, Nam H, et al. Feedback regulation via AMPK and HIF-1 mediates ROS-dependent longevity in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 2014;111:E4458-67 pubmed publisher
    ..Thus, AMPK and HIF-1 may control immunity and longevity tightly by acting as feedback regulators of ROS. ..
  22. Luhachack L, Visvikis O, Wollenberg A, Lacy Hulbert A, Stuart L, Irazoqui J. EGL-9 controls C. elegans host defense specificity through prolyl hydroxylation-dependent and -independent HIF-1 pathways. PLoS Pathog. 2012;8:e1002798 pubmed publisher
    ..Together, our observations show that HIF can set the balance between alternative pathogen-specific host responses, potentially acting as an evolutionarily conserved specificity switch in the host innate immune response. ..
  23. Budde M, Roth M. The response of Caenorhabditis elegans to hydrogen sulfide and hydrogen cyanide. Genetics. 2011;189:521-32 pubmed publisher
    ..Our results suggest the hypoxia-independent hif-1 response in C. elegans evolved to respond to the naturally occurring small molecules H2S and HCN...
  24. Katschinski D, Glueck S. Hot worms can handle heavy metal. Focus on "HIF-1 is required for heat acclimation in the nematode Caenorhabditis elegans". Physiol Genomics. 2003;14:1-2 pubmed