Biosynthesis, remodeling and turnover of mitochondrial cardiolipin

Abstract

Among mitochondrial lipids, cardiolipin occupies a unique place. It is the only phospholipid that is specific to mitochondria and although it is merely a minor component, accounting for 10-20% of the total phospholipid content, cardiolipin plays an important role in the molecular organization, and thus the function of the cristae. This review covers the formation of cardiolipin, a phospholipid dimer containing two phosphatidyl residues, and its assembly into mitochondrial membranes. While a large body of literature exists on this topic, the review focuses on papers that appeared in the past three years. This article is part of a Special Issue entitled: Lipids of Mitochondria edited by Guenther Daum.

Keywords: Lipids; Membrane assembly; Metabolism; Mitochondria.

Figure 1. Cardiolipin biosynthesis in mitochondria

Glycero-3-phosphate (G3P) is acylated to lysophosphatidic acid (LPA) and then to phosphatidic acid (PA). PA formation occurs on the outer face of the outer mitochondrial membrane (OM) and in the endoplasmic reticulum. PA is transferred from the outer to the inner mitochondrial membrane (IM) via the intermembrane space (IMS) and is converted to CL on the matrix face of the IM via the intermedates CDPdiacylglycerol (CDP-DG), phosphatidylglycerophosphate (PGP), and phosphatidylglycerol (PG). The final step of the pathway is the remodeling of nascent cardiolipin (CL_n) to mature cardiolipin (CL_m). Remodeling occurs in the outer leaflet of the inner membrane and requires disturbance of the bilayer packing order. Mammalian genes are shown for the enzymes of PA synthesis and yeast genes are shown for all other enzymes.