The hypoxia response pathway promotes PEP carboxykinase and gluconeogenesis in C. elegans.
In: Nature Communications, Jg. 13 (2022-10-18), Heft 1, S. 1-15
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Zugriff:
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. The hypoxia response pathway can counter pathological damage caused by low oxygen availability. Here the authors employ a multiomics approach to show how the pathway reprograms metabolism towards gluconeogenesis to combat oxidative stress. [ABSTRACT FROM AUTHOR]
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The hypoxia response pathway promotes PEP carboxykinase and gluconeogenesis in C. elegans.
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Autor/in / Beteiligte Person: | Vora, Mehul ; Pyonteck, Stephanie M. ; Popovitchenko, Tatiana ; Matlack, Tarmie L. ; Prashar, Aparna ; Kane, Nanci S. ; Favate, John ; Shah, Premal ; Rongo, Christopher |
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Zeitschrift: | Nature Communications, Jg. 13 (2022-10-18), Heft 1, S. 1-15 |
Veröffentlichung: | 2022 |
Medientyp: | academicJournal |
ISSN: | 2041-1723 (print) |
DOI: | 10.1038/s41467-022-33849-x |
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