Identification of a Cardiolipin-specific Phospholipase Encoded by the Gene CLD1 (YGR110W) in Yeast

• Published in: The Journal of biological chemistry Vol. 284; no. 17; pp. 11572 - 11578
• Main Authors: Beranek, Andreas, Rechberger, Gerald, Knauer, Heide, Wolinski, Heimo, Kohlwein, Sepp.D., Leber, Regina
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 24.04.2009; American Society for Biochemistry and Molecular Biology
• Subjects: Cardiolipins - chemistry; Cardiolipins - metabolism; Cardiolipins - physiology; Catalysis; Dimerization; Escherichia coli - metabolism; Fatty Acids, Unsaturated - metabolism; Humans; Lipids - chemistry; Lipids and Lipoproteins: Metabolism, Regulation, and Signaling; Lysophospholipids - chemistry; Lysophospholipids - metabolism; Mitochondria - metabolism; Models, Biological; Mutation; Open Reading Frames; Phospholipases - metabolism; Protein Structure, Tertiary; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - metabolism; Temperature
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M805511200

The mitochondrial dimeric phospholipid cardiolipin is characterized by a high degree of unsaturation of its acyl chains, which is important for its functional interaction with mitochondrial enzymes. The unusual fatty acid composition of cardiolipin molecular species emerges from a de novo synthesized “premature” species by extensive acyl chain remodeling that involves as yet only partially identified acyltransferases and phospholipases. Recently, the yeast protein Taz1p was shown to function as a transacylase, which catalyzes the reacylation of monolysocardiolipin to mature cardiolipin. A defect in the orthologous human TAZ gene is associated with Barth syndrome, a severe genetic disorder, which may lead to cardiac failure and death in childhood. We now identified the protein encoded by reading frame YGR110W as a mitochondrial phospholipase, which deacylates de novo synthesized cardiolipin. Ygr110wp has a strong substrate preference for palmitic acid residues and functions upstream of Taz1p, to generate monolysocardiolipin for Taz1p-dependent reacylation with unsaturated fatty acids. We therefore rename the Ygr110wp as Cld1p (cardiolipin-specific deacylase 1).