Submitted on October 30, 2007
Revised on December 7, 2007
Accepted on December 11, 2007
Cardiolipin synthesis for the assembly of bacterial and mitochondrial membranes
Michael Schlame
Anesthesiology, NYU School of Medicine, New York, NY 10016
Corresponding Author: michael.schlame{at}med.nyu.edu
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 analogues 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, the 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.
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