Cardiolipin molecular species with shorter acyl chains accumulate in Saccharomyces cerevisiae mutants lacking the acyl coenzyme A-binding protein Acb1p: new insights into acyl chain remodeling of cardiolipin.
The function of the mitochondrial phospholipid cardiolipin (CL) is thought to depend on its acyl chain composition. The present study aims at a better understanding of the way the CL species profile is established in Saccharomyces cerevisiae by using depletion of the acyl-CoA-binding protein Acb1p as a tool to modulate the cellular acyl chain content. Despite the presence of an intact CL remodeling system, acyl chains shorter than 16 carbon atoms (C16) were found to accumulate in CL in cells lacking Acb1p. Further experiments revealed that Taz1p, a key CL remodeling enzyme, was not responsible for the shortening of CL in the absence of Acb1p. This left de novo CL synthesis as the only possible source of acyl chains shorter than C16 in CL. Experiments in which the substrate specificity of the yeast cardiolipin synthase Crd1p and the acyl chain composition of individual short CL species were investigated, indicated that both CL precursors (i.e. phosphatidylglycerol and CDP-diacylglycerol) contribute to comparable extents to the shorter acyl chains in CL in acb1 mutants. Based on the findings, we conclude that the fatty acid composition of mature CL in yeast is governed by the substrate specificity of the CL-specific lipase Cld1p and the fatty acid composition of the Taz1p substrates.
Rijken
Pieter J
PJ
Department of Biochemistry of Membranes, Bijvoet Institute and Institute of Biomembranes, Utrecht University, 3584 CH Utrecht, The Netherlands.
Houtkooper
Riekelt H
RH
Akbari
Hana
H
Brouwers
Jos F
JF
Koorengevel
Martijn C
MC
de Kruijff
Ben
B
Frentzen
Margrit
M
Vaz
Frédéric M
FM
de Kroon
Anton I P M
AI
D000217:Acyltransferases / Q000378:metabolism; D002308:Cardiolipins / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003567:Cytidine Diphosphate Diglycerides / Q000378:metabolism; D013058:Mass Spectrometry; D009154:Mutation; D010715:Phosphatidylglycerols / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion
C492820:ACB1 protein, S cerevisiae; D002308:Cardiolipins; D002352:Carrier Proteins; D003567:Cytidine Diphosphate Diglycerides; D010715:Phosphatidylglycerols; D029701:Saccharomyces cerevisiae Proteins; D000217:Acyltransferases; C481660:Taz1 protein, S cerevisiae