Regulation of glycolysis by the hypoxia-inducible factor (HIF): implications for cellular physiology

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-1 alpha (HIF-1 alpha) 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-1 alpha in the regulation of hypoxic glycolysis and its implications for physiological processes such as angiogenesis and immune cell effector function.

Automated summary

Under hypoxic conditions, eukaryotic cells can shift metabolism towards glycolysis to maintain ATP levels, a process regulated by HIF-1 alpha. This metabolic switch is crucial for cellular survival during acute hypoxic stress and has implications for cancer cell survival and growth. Understanding the mechanisms central to this reprogramming is important for both physiological and pathophysiological processes.