Mitochondrial membrane lipid remodeling in pathophysiology: a new target for diet and therapeutic interventions

Abstract

Mitochondria are arbiters in the fragile balance between cell life and death. These organelles present an intricate membrane system, with a peculiar lipid composition and displaying transverse as well as lateral asymmetry. Some lipids are synthesized inside mitochondria, while others have to be imported or acquired in the form of precursors. Here, we review different processes, including external interventions (e.g., diet) and a range of biological events (apoptosis, disease and aging), which may result in alterations of mitochondrial membrane lipid content. Cardiolipin, the mitochondria lipid trademark, whose biosynthetic pathway is highly regulated, will deserve special attention in this review. The modulation of mitochondrial membrane lipid composition, especially by diet, as a therapeutic strategy for the treatment of some pathologies will be also addressed.

Keywords: AIF; ATP; Aging; Apoptosis; BTHS; Barth syndrome; CL; Cardiolipin; DNA; DOX; ER; GD3; IMM; MAM; MLCL; MPT; Mitochondrial membrane lipids; OMM; PC; PE; PG; PI; PS; PTP; PUFA; Pathology; ROS; Smac/DIABLO; UCP; adenosine triphosphate; apoptosis-inducing factor; calcium-independent phospholipase A2γ; cardiolipin; cyt c; cytochrome c; deoxyribonucleic acid; doxorubicin; endoplasmic reticulum; ganglioside GD3; iPLA2γ; inner mitochondrial membrane; mitochondria-associated membrane; mitochondrial DNA; mitochondrial permeability transition; mitochondrial permeability transition pore; monolysocardiolipin; mtDNA; outer mitochondrial membrane; phosphatidylcholine; phosphatidylethanolamine; phosphatidylglycerol; phosphatidylinositol; phosphatidylserine; polyunsaturated fatty acid; reactive oxygen species; second mitochondria-derived activator of caspases/direct IAP binding protein with low Pi; uncoupling protein.