Very-long-chain fatty acid-containing phospholipids accumulate in fatty acid synthase temperature-sensitive mutant strains of the fission yeast Schizosaccharomyces pombe fas2/lsd1

Fission yeast Isd1 strains show aberrant mitosis with a Isd phenotype, larg e and small daughter nuclei, and a very thick septum, the phenotypic expres sion being temperature-sensitive. The Isd1(+) gene is the homologue of the budding yeast FAS2 gene encoding the fatty acid synthase alpha -subunit as reported previously (S. Saitoh, K. Takahashi, K. Nabeshima, Y. Yamashita, Y . Nakaseko, A. Hirata, M. Yanagida, J. Cell Biol. 134 (1996) 949-961). In t his paper, Isd1 is considered to represent fas2. Here, three fas2 strains w ere investigated and found to have missense point mutations at different si tes in the,gene encoding the alpha -subunit of fatty acid synthase. The mut ation affected only slightly the enzymatic activities monitored in vitro. U nexpectedly, abnormal phospholipids, phosphatidyleholine and phosphatidylet hanolamine, both of which contain a very-long-chain fatty acyl residue (1-m elissoyl-2-oleolyl-sn-glycero-3-phosphocholine and 1-melissoyl-2-oleolyl-sn -glycero-3-phosphoethanolamine), accumulated in fas2 strains in a temperatu re-sensitive manner. Rescue of the fas2 strains by addition of palmitate to the medium at restrictive temperature was accompanied by disappearance of these abnormal phospholipids. Accumulation of these lipids in membranes may cause alteration of various cellular functions. (C) 2001 Published by Else vier Science B.V.