ArticleNature communications2022
The hypoxia response pathway promotes PEP carboxykinase and gluconeogenesis in C. elegans.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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27 citing papers in PubMed, 52 citations in OpenAlex.
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- Targeting Mitochondrial Stress Responses: Terbinafine and Miglustat as Novel Lifespan and Healthspan Modulators.Aging cell · 2026Article
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- High confidence HIF-1 target genes for quantifying the activation of the HIF-1-mediated hypoxia response.microPublication biology · 2026Article
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- OSM-11 modulates salinity-stress tolerance inbioRxiv : the preprint server for biology · 2025Article
- TheInternational journal of molecular sciences · 2025Article
- Conserved lipid metabolic reprogramming confers hypoxic and aging resilience.bioRxiv : the preprint server for biology · 2025Article
- The Hypoglycemic Activity ofGels (Basel, Switzerland) · 2025Article
- Suppressing APOE4-induced neural pathologies by targeting the VHL-HIF axis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
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- Genome-wide analysis of Smad and Schnurri transcription factors inbioRxiv : the preprint server for biology · 2025Article
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- Enhancing intraneural revascularization following peripheral nerve injury through hypoxic Schwann-cell-derived exosomes: an insight into endothelial glycolysis.Journal of nanobiotechnology · 2024Article
- Suppressing APOE4-induced mortality and cellular damage by targeting VHL.bioRxiv : the preprint server for biology · 2024Article
- Hypoxia-inducible factor induces cysteine dioxygenase and promotes cysteine homeostasis ineLife · 2024Article
- Transcriptome analyses describe the consequences of persistent HIF-1 over-activation in Caenorhabditis elegans.PloS one · 2024Article
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9 authors at 1 institution in 1 country.
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Abstract
Actively dividing cells, including some cancers, rely on aerobic glycolysis rather than oxidative phosphorylation to generate energy, a phenomenon termed the Warburg effect. Constitutive activation of the Hypoxia Inducible Factor (HIF-1), a transcription factor known for mediating an adaptive response to oxygen deprivation (hypoxia), is a hallmark of the Warburg effect. HIF-1 is thought to promote glycolysis and suppress oxidative phosphorylation. Here, we instead show that HIF-1 can promote gluconeogenesis. Using a multiomics approach, we reveal the genomic, transcriptomic, and metabolomic landscapes regulated by constitutively active HIF-1 in C. elegans. We use RNA-seq and ChIP-seq under aerobic conditions to analyze mutants lacking EGL-9, a key negative regulator of HIF-1. We integrate these approaches to identify over two hundred genes directly and functionally upregulated by HIF-1, including the PEP carboxykinase PCK-1, a rate-limiting mediator of gluconeogenesis. This activation of PCK-1 by HIF-1 promotes survival in response to both oxidative and hypoxic stress. Our work identifies functional direct targets of HIF-1 in vivo, comprehensively describing the metabolome induced by HIF-1 activation in an organism.
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