Hypometabolic Responses to Chronic Hypoxia: A Potential Role for Membrane Lipids

Abstract

Metabolic suppression is an essential strategy to cope with chronic hypoxia. This review examines the physiological processes used to survive in low oxygen environments. It proposes a novel mechanism–the remodeling of membrane lipids–to suppress ATP use and production. Temperature (homeoviscous adaptation), diet (natural doping in migrant birds) and body mass (membrane pacemaker of metabolism) have an impact on the lipid composition of membranes, which, in turn, modulates metabolic capacity. Vertebrate champions of hypoxia tolerance show extensive changes in membrane lipids upon in vivo exposure to low oxygen. These changes and those observed in hibernating mammals can promote the downregulation of ion pumps (major ATP consumers), ion channels, mitochondrial respiration capacity (state 3, proton leak, cytochrome c oxidase), and energy metabolism (β-oxidation and glycolysis). A common membrane signal regulating the joint inhibition of ion pumps and channels could be an exquisite way to preserve the balance between ATP supply and demand in hypometabolic states. Membrane remodeling together with more traditional mechanisms could work in concert to cause metabolic suppression.

Epigenetic and post-transcriptional repression support metabolic suppression in chronically hypoxic goldfish

“…In contrast to protein-coding genes, the relative abundance of the evolutionarily conserved miRNA-122-5p is not affected by chronic hypoxia. The transcriptional regulation of these key genes involved in cholesterol metabolism clearly support reported changes in membrane cholesterol composition, a newly proposed mechanism of metabolic suppression 86 .…”