Thematic Review Series: Glycerolipids. Cardiolipin synthesis for the assembly of bacterial and mitochondrial membranes

Abstract

In this article, the formation of prokaryotic and eukaryotic cardiolipin is reviewed in light of its biological function. I begin with a detailed account of the structure of cardiolipin, its stereochemistry, and the resulting physical properties, and I present structural analogs of cardiolipin that occur in some organisms. Then I continue to discuss i) the de novo formation of cardiolipin, ii) its acyl remodeling, iii) the assembly of cardiolipin into biological membranes, and iv) the degradation of cardiolipin, which may be involved in apoptosis and mitochondrial fusion. Thus, this article covers the entire metabolic cycle of this unique phospholipid. It is shown that mitochondria produce cardiolipin species with a high degree of structural uniformity and molecular symmetry, among which there is often a dominant form with four identical acyl chains. The subsequent assembly of cardiolipin into functional membranes is largely unknown, but the analysis of crystal structures of membrane proteins has revealed a first glimpse into the underlying principles of cardiolipin-protein interactions. Disturbances of cardiolipin metabolism are crucial in the pathophysiology of human Barth syndrome and perhaps also play a role in diabetes and ischemic heart disease.-Schlame, M. Cardiolipin synthesis for the assembly of bacterial and mitochondrial membranes.

PhoPQ regulates acidic glycerophospholipid content of the Salmonella Typhimurium outer membrane

“…It is tempting to speculate that modified lipid A structures require specific increases in CL to maintain proper membrane curvature during bacterial replication. Cardiolipin species are also known to interact with cationic amphipathic helical protein segments on bilayer surfaces (32). Therefore, CL molecules may direct CAMP, or cell division components, to specific microdomains to increase bacterial resistance, or coordinate membrane fission with OM lipid A and PG remodeling.…”

Negatively Charged Lipids as a Potential Target for New Amphiphilic Aminoglycoside Antibiotics

“…Even fatty acid chain identity is highly variable; cardiolipin is characterized by a high degree of chain unsaturation (14,(55)(56)(57) and a global negative spontaneous curvature (58 -60). In turn, cardiolipin leads to highly bent structures and domains in disordered phases.…”

“…Cardiolipin has been described for its predisposition to be organized into clusters (12). This structurally unusual phospholipid carries two negative charges (13) due to its dimeric structure consisting of two phosphatidyl residues connected by a glycerol bridge and four associated fatty acyl chains, which are characterized by a high degree of symmetry and unsaturation (14). Cardiolipin is known for its sensitivity to stressors, such as the addition of organic solvents, high salt content, or quaternary ammonium compounds (15).…”

Aromatic residues at the edge of the antibody combining site facilitate viral glycoprotein recognition through membrane interactions

“…CL, or diphosphatidylglycerol, is a "double" phospholipid with two negatively charged headgroups and four acyl chains that exhibits a single negative charge at neutral pH. In humans, CL distribution is limited to those membranes and tissues where CL synthetases are found (i.e., mitochondrial membranes and mitochondria-rich tissue) (42). The reason for including CL in our previous analysis of 2F5 and 4E10 lipid reactivity relates to the suggestion that 2F5 and 4E10 are autoantibodies specific for CL (25), a hypothesis that will be elaborated on further in Discussion.…”