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 O 2 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. © 2011 Springer Science+Business Media, LLC.