Identification of a cardiolipin-specific phospholipase encoded by the gene CLD1 (YGR110W) in yeast.
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).
Beranek
Andreas
A
Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50/II, Graz A-8010, Austria.
Rechberger
Gerald
G
Knauer
Heide
H
Wolinski
Heimo
H
Kohlwein
Sepp D
SD
Leber
Regina
R
D002308:Cardiolipins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D002384:Catalysis; D019281:Dimerization; D004926:Escherichia coli / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008246:Lysophospholipids / Q000737:chemistry* / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D016366:Open Reading Frames; D010740:Phospholipases / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D013696:Temperature
D002308:Cardiolipins; D005231:Fatty Acids, Unsaturated; D008055:Lipids; D008246:Lysophospholipids; D029701:Saccharomyces cerevisiae Proteins; C067188:monolysocardiolipin; C585646:CLD1 protein, S cerevisiae; D010740:Phospholipases