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Vol. 12, Issue 4, 1147-1160, April 2001

Depletion of Acyl-Coenzyme A-Binding Protein Affects Sphingolipid Synthesis and Causes Vesicle Accumulation and Membrane Defects in Saccharomyces cerevisiae

Barbara Gaigg,^* Thomas B. F. Neergaard,^* Roger Schneiter, Jan Krogh Hansen,^* Nils J. Færgeman,^* Niels A. Jensen,^* Jens R. Andersen,^* Jørgen Friis,^* Roger Sandhoff,^§ Henrik Daa Schrøder, and Jens Knudsen^*¶

 ^*Department of Biochemistry and Molecular Biology,  Institute of Pathology, University of Southern Denmark, Odense University, DK-5230 Odense M, Denmark;  Institute of Biochemistry, Graz, University of Technology, A-8010 Graz, Austria; and  ^§German Cancer Research Center, 69120 Heidelberg, Germany

Deletion of the yeast gene ACB1 encoding Acb1p, the yeast homologue of the acyl-CoA-binding protein (ACBP), resulted in a slower growing phenotype that adapted into a faster growing phenotype with a frequency >1:10⁵. A conditional knockout strain (Y700pGAL1-ACB1) with the ACB1 gene under control of the GAL1 promoter exhibited an altered acyl-CoA profile with a threefold increase in the relative content of C18:0-CoA, without affecting total acyl-CoA level as previously reported for an adapted acb1 strain. Depletion of Acb1p did not affect the general phospholipid pattern, the rate of phospholipid synthesis, or the turnover of individual phospholipid classes, indicating that Acb1p is not required for general glycerolipid synthesis. In contrast, cells depleted for Acb1p showed a dramatically reduced content of C26:0 in total fatty acids and the sphingolipid synthesis was reduced by 50-70%. The reduced incorporation of [³H]myo-inositol into sphingolipids was due to a reduced incorporation into inositol-phosphoceramide and mannose-inositol-phosphoceramide only, a pattern that is characteristic for cells with aberrant endoplasmic reticulum to Golgi transport. The plasma membrane of the Acb1p-depleted strain contained increased levels of inositol-phosphoceramide and mannose-inositol-phosphoceramide and lysophospholipids. Acb1p-depleted cells accumulated 50- to 60-nm vesicles and autophagocytotic like bodies and showed strongly perturbed plasma membrane structures. The present results strongly suggest that Acb1p plays an important role in fatty acid elongation and membrane assembly and organization.

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These authors contributed equally to the experimental work performed.

^¶ Corresponding author. E-mail: jkk{at}bmb.sdu.dk.

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Molecular Biology of the Cell
Vol. 12, 1147-1160, April 2001
Copyright © 2001 by The American Society for Cell Biology

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