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.
Highlights
DE NOVO FORMATION OF CARDIOLIPINThe biosynthesis of cardiolipin begins with the formation of phosphatidic acid from glycerol-3-phosphate and activated fatty acids
In this article, the formation of prokaryotic and eukaryotic cardiolipin is reviewed in light of its biological function
The apparent acyl specificity of cardiolipin synthase from humans [44], rat [50, 51], and Arabidopsis [43] has been measured with various molecular species of phosphatidyl-CMP and phosphatidylglycerol. These experiments have clearly established that cardiolipin synthase does not possess the necessary acyl specificity to explain the preferential synthesis of tetralinoleoylcardiolipin, the dominant molecular species in many animal and plant tissues, suggesting that another mechanism must exist
Summary
The biosynthesis of cardiolipin begins with the formation of phosphatidic acid from glycerol-3-phosphate and activated fatty acids. Phosphatidic acid reacts with CTP to form the high-energy phosphoanhydride intermediate phosphatidyl-CMP. Phosphatidylglycerol receives a phosphatidyl group from another phosphatidylglycerol by transesterification, catalyzed by a phospholipase D-type enzyme. Phosphatidylglycerol receives an activated phosphatidyl group from phosphatidyl-CMP, which is catalyzed by an enzyme that falls into the category of phosphatidyltransferases (Fig. 4). Enzymes of this category produce phosphatidylserine, phosphatidylinositol, and phosphatidylglycerol. The prokaryotic formation of cardiolipin is a near-equilibrium reaction, whereas the eukaryotic formation has a considerable negative change in free energy
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
