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 lsd1 strains show aberrant mitosis with a lsd phenotype, large and small daughter nuclei, and a very thick septum, the phenotypic expression being temperature-sensitive. The lsd1(+) 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 this paper, lsd1 is considered to represent fas2. Here, three fas2 strains were investigated and found to have missense point mutations at different sites in the gene encoding the alpha-subunit of fatty acid synthase. The mutation affected only slightly the enzymatic activities monitored in vitro. Unexpectedly, abnormal phospholipids, phosphatidylcholine and phosphatidylethanolamine, both of which contain a very-long-chain fatty acyl residue (1-melissoyl-2-oleolyl-sn-glycero-3-phosphocholine and 1-melissoyl-2-oleolyl-sn-glycero-3-phosphoethanolamine), accumulated in fas2 strains in a temperature-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.
Yokoyama
K
K
Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa, Japan. yokoyama@physiol1.utmem.edu
Saitoh
S
S
Ishida
M
M
Yamakawa
Y
Y
Nakamura
K
K
Inoue
K
K
Taguchi
R
R
Tokumura
A
A
Nishijima
M
M
Yanagida
M
M
Setaka
M
M
D002250:Carbon Radioisotopes; D002855:Chromatography, Thin Layer; D064429:Fatty Acid Synthases / Q000032:analysis / Q000235:genetics*; D005227:Fatty Acids / Q000737:chemistry*; D008401:Gas Chromatography-Mass Spectrometry; D009154:Mutation; D010743:Phospholipids / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D013696:Temperature
D002250:Carbon Radioisotopes; D005227:Fatty Acids; D010743:Phospholipids; D064429:Fatty Acid Synthases