Mechanisms of sensing and adaptive responses to low oxygen conditions in mammals and yeasts.

Abstract

Oxygen is required for effective production of ATP and plays a key role in the maintenance of life for all organisms, excepting strict anaerobes. The ability of aerobic organisms to sense and respond to changes in oxygen level is a basic requirement for their survival. Eukaryotes have developed adaptive mechanisms to sense and respond to decreased oxygen concentrations (hypoxia) through adjustment of oxygen homeostasis by upregulating hypoxic and downregulating aerobic nuclear genes. This review summarizes recent data on mechanisms of cells sensing and responding to changes in oxygen availability in mammals and in yeasts. In the first part of the review, prominence is given to functional regulation and stabilization of hypoxia-inducible factors (HIFs), HIF-mediated regulation of electron transport flux and repression of lipogenesis, as well as to hypoxia-induced mitochondrial permeability transition (pore) opening, cell death, and autophagy. In the second part of the review emphasis is placed on oxygen sensing in nonpathogenic yeasts by heme, unsaturated fatty acids, and sterols, as well as on responses to hypoxia in fungal pathogens.