Impact of Intracellular Diffusion of Oxygen in Hypoxic Sensing

Abstract

Hypoxia-inducible factor 1 (HIF-1) is the key to genetic adaptations to hypoxia in eukaryotes. In vivo, capillary pO₂ and extracellular- and intracellular- O₂ gradients define pO2 at the O₂ labile subunit HIF-1α.With a novel technique for subcellular imaging of O₂ heterogeneity using GFP, the present study was undertaken to examine the possibility that changes in mitochondrial respiration significantly affect intracellular O₂ gradients and thus, HIF-1 expression.We failed to demonstrate consistent changes in intracellular O₂ distributions in cultured cells with different metabolic and morphological properties (COS-7, Hep G2, and Hep3B cells) while mitochondrial O₂ consumptionwaswidely changed at 1%O₂.Thus,we conclude that conductance for intracellular diffusion of O₂ is high in these cells and intracellular O₂ gradients might not be involved in the regulation of HIF-1 expression in vivo.