Redefining the role of hypoxia-inducible factors (HIFs) in oxygen homeostasis.

ABSTRACT: Hypoxia-inducible factors (HIFs) are key regulators of intracellular oxygen homeostasis. The marked increase in HIFs activity in hypoxia as compared to normoxia, together with their transcriptional control of primary metabolic pathways, motivated the widespread view of HIFs as responsible for the cell's metabolic adaptation to hypoxic stress. In this work, we suggest that this prevailing model of HIFs regulation is misleading. We propose an alternative model focused on understanding the dynamics of HIFs' activity within its physiological context. Our model suggests that HIFs would not respond to but rather prevent the onset of hypoxic stress by regulating the traffic of electrons between catabolic substrates and oxygen. The explanatory power of our approach is patent in its interpretation

SUBMITTER: Arias CF 

PROVIDER: S-EPMC11910619 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature