Role of the HIF oxygen sensing pathway in cell defense and proliferation through the control of amino acid metabolism

• Published in: Biochimica et biophysica acta. Molecular cell research 2020-09, Vol.1867 (9), p.118733-118733, Article 118733
• Main Authors: Bouthelier, Antonio, Aragonés, Julián
• Format: Article
• Language: English
• Subjects: Amino acid metabolism; Amino Acids - metabolism; Animals; Cell Proliferation; Citric Acid Cycle; Collagen - metabolism; Glutamine - metabolism; Glutathione - metabolism; HIF; Humans; Hypoxia - metabolism; Hypoxia-Inducible Factor 1 - metabolism; Hypoxia-inducible factors; mTORC1; Oxidation-Reduction; Oxidative Stress; Oxygen - metabolism; Proliferation; Redox stress; Signal Transduction
• ISSN: 0167-4889; 1879-2596
• DOI: 10.1016/j.bbamcr.2020.118733

Cell responses to reduced oxygen supply (hypoxia) are largely mediated by hypoxia-inducible transcription factors (HIFs). The pathophysiological role of the HIF pathway is driven by its ability to potentiate key biological processes as part of the adaptation to hypoxia, such as erythropoiesis and angiogenesis. Moreover, the role of HIF signaling in the reprogramming of cell metabolism is also critical to understand the role of these transcription factors in health and disease. In this regard, HIFs reprogram oxidative metabolism of glucose and fatty acids, offering a molecular mechanism by which the HIF pathway can help cells become more tolerant of redox stress during hypoxic/ischemic episodes. However, the way in which HIFs influence amino acid metabolism and its pathophysiology consequences have been less well explored. Here we review recent studies about the role of the HIF1α and HIF2α isoforms in amino acid metabolism, which provides insight to better understand how these factors can influence cell autonomous proliferation and cellular tolerance to hypoxia. •The HIF pathway induces cellular defense by promoting glutathione biosynthesis.•The HIF pathway reprogram glutamine oxidative and reductive metabolism.•HIF1α reduces cell proliferation by rewiring glutamine and glucose metabolism.•HIF2α favors mTORC1 activation through key amino acid carriers.