Apoptosis-induced changes in mitochondrial lipids

Apoptosis is an active and tightly regulated form of cell death, which can also be considered a stress-induced process of cellular communication. Recent studies reveal that the lipid network within cells is involved in the regulation and propagation of death signalling. Despite the vast growth of our current knowledge on apoptosis, little is known of the specific role played by lipid molecules in the central event of apoptosis—the piercing of mitochondrial membranes. Here we review the information regarding changes in mitochondrial lipids that are associated with apoptosis and discuss whether they may be involved in the permeabilization of mitochondria to release their apoptogenic factors, or just lie downstream of this permeabilization leading to the amplification of caspase activation. We focus on the earliest changes that physiological apoptosis induces in mitochondrial membranes, which may derive from an upstream alteration of phospholipid metabolism that reverberates on the mitochondrial re-modelling of their characteristic lipid, cardiolipin. Hopefully, this review will lead to an increased understanding of the role of mitochondrial lipids in apoptosis and also help revealing new stress sensing mechanisms in cells. This article is part of a Special Issue entitled Mitochondria: the deadly organelle. ⺠After apoptosis induction, the initial lipid changes occurring in mitochondria appear to reflect an upstream deficiency in the biosynthesis of phospholipids including cardiolipin. ⺠Lysolipids are prominent among these initial changes and may facilitate the pro-apoptotic action of Bax and Bak that produces the piercing of mitochondria. ⺠Pro-apoptotic Bid provides a link between phospholipid deficiency and mitochondrial membranes by transporting lysolipids and binding to cardiolipin, affecting its re-modelling. ⺠Other changes in membrane lipids generally occur after the piercing of the outer mitochondrial membrane has occurred.