HIF1α-dependent uncoupling of glycolysis suppresses tumor cell proliferation.

ABSTRACT: Hypoxia-inducible factor-1α (HIF1α) attenuates mitochondrial activity while promoting glycolysis. However, lower glycolysis is compromised in human clear cell renal cell carcinomas, in which HIF1α acts as a tumor suppressor by inhibiting cell-autonomous proliferation. Here, we find that, unexpectedly, HIF1α suppresses lower glycolysis after the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) step, leading to reduced lactate secretion in different tumor cell types when cells encounter a limited pyruvate supply such as that typically found in the tumor microenvironment in vivo. This is because HIF1α-dependent attenuation of mitochondrial oxygen consumption increases the NADH/NAD⁺ ratio that suppresses the activity of the NADH-sensitive GAPDH glycolytic enzyme. This is manifested

SUBMITTER: Urrutia AA 

PROVIDER: S-EPMC11063627 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature