Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland.
School of Medicine, University College Dublin, Belfield, Dublin, Ireland.
J Physiol. 2021 Jan;599(1):23-37. doi: 10.1113/JP280572. Epub 2020 Oct 15.
Under conditions of hypoxia, most eukaryotic cells can shift their primary metabolic strategy from predominantly mitochondrial respiration towards increased glycolysis to maintain ATP levels. This hypoxia-induced reprogramming of metabolism is key to satisfying cellular energetic requirements during acute hypoxic stress. At a transcriptional level, this metabolic switch can be regulated by several pathways including the hypoxia inducible factor-1α (HIF-1α) which induces an increased expression of glycolytic enzymes. While this increase in glycolytic flux is beneficial for maintaining bioenergetic homeostasis during hypoxia, the pathways mediating this increase can also be exploited by cancer cells to promote tumour survival and growth, an area which has been extensively studied. It has recently become appreciated that increased glycolytic metabolism in hypoxia may also have profound effects on cellular physiology in hypoxic immune and endothelial cells. Therefore, understanding the mechanisms central to mediating this reprogramming are of importance from both physiological and pathophysiological standpoints. In this review, we highlight the role of HIF-1α in the regulation of hypoxic glycolysis and its implications for physiological processes such as angiogenesis and immune cell effector function.
在缺氧条件下，大多数真核细胞可以将其主要代谢策略从主要的线粒体呼吸转变为增加的糖酵解，以维持 ATP 水平。这种缺氧诱导的代谢重编程是满足急性缺氧应激期间细胞能量需求的关键。在转录水平上，这种代谢转换可以通过几种途径进行调节，包括缺氧诱导因子-1α（HIF-1α），它诱导糖酵解酶的表达增加。虽然这种糖酵解通量的增加有利于在缺氧期间维持生物能量稳态，但介导这种增加的途径也可以被癌细胞利用，以促进肿瘤的存活和生长，这一领域已经得到了广泛的研究。最近人们认识到，缺氧时糖酵解代谢的增加也可能对缺氧免疫和内皮细胞的细胞生理学产生深远影响。因此，从生理和病理生理的角度来看，理解介导这种重编程的核心机制非常重要。在这篇综述中，我们强调了 HIF-1α 在调节缺氧糖酵解及其对血管生成和免疫细胞效应功能等生理过程中的作用。
