Organelle Structure, Function, and Inheritance in Yeast: A Role for Fatty Acid Synthesis?

of medium chain fatty acids (MCFAs; C 8 –C 12) requires their activation inside peroxisomes by an acyl-CoA syn-SFB Biomembrane Research Center Institut fü r Biochemie und Lebensmittelchemie thetase, Faa2p. Myristoylation of membrane-associated proteins is catalyzed by Nmt1p (for review on lipid syn-Technische Universitä t Graz Petersgasse 12 thesis in yeast, see Kohlwein et al., 1996). S. cerevisiae Fatty Acid Synthesis Mutants A-8010 Graz Austria Mutants defective in fatty acid synthesis were isolated in the early 1970s in screens for cells that can grow only when fatty acids are added to the growth medium. All the mutants selected by this approach, ole1, fas1, fas2, Although fatty acids are generally acknowledged to be acc1, and acc2 (defective in apoenzyme-biotin ligase) essential, impaired fatty acid biosynthesis is not readily were completely rescued by appropriate fatty acid sup-associated with morphological defects. This view has plementation. Subsequent cloning and disruption of been changed by two recent studies of conditional yeast acetyl-CoA carboxylase, however, revealed that cells mutants that affect key steps of fatty acid synthesis. lacking Acc1p are not viable even if fatty acids are sup-Characteristically, these mutants were isolated in plemented (Hasslacher et al., 1993). This observation screens unrelated to lipid metabolism (Table 1). This suggested that acetyl-CoA carboxylase performs a sec-minireview focuses on the link between fatty acid syn-ond essential function in addition to the synthesis of thesis and organelle structure, function, and inheritance LCFAs. (Warren and Wickner, 1996). Whether this link is a direct Confirming this conclusion, Tartakoff and collabora-one or, instead, the observed phenotypes are indirect tors isolated a temperature-sensitive allele of acetyl-manifestations of a cell that fails to properly synthesize CoA carboxylase (mtr7) that is not rescued by LCFA and assemble its membrane components, however, is supplementation (Schneiter et al., 1996). mtr7 cells ac-not yet resolved. We describe the newly discovered cumulate nuclear poly(A) ϩ RNA (mRNA transport mu-mutant phenotypes in the context of earlier observations tants), suggesting that the nonsupplementable function that fatty acid desaturation is required for mitochondrial of acetyl-CoA carboxylase is directly or indirectly related movement and inheritance and that the addition of acti-to the structure and function of the nuclear envelope/ vated fatty acids to a reconstituted secretory transport nuclear pore complex. Unlike the fatty acid auxotrophic assay promotes vesicle budding and fusion. In an at-acetyl-CoA carboxylase mutant cells, mtr7 cells display tempt to correlate the different mutant phenotypes, we a striking separation of inner …