Functional differentiation and selective inactivation of multiple Saccharomyces cerevisiae genes involved in very-long-chain fatty acid synthesis

Rössler, H; Rieck, Christoph; Delong, Thomas; Hoja, Ursula; Schweizer, Eckhart

doi:10.1007/s00438-003-0836-0

Cited by 61 publications

(39 citation statements)

References 26 publications

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“…Consistently, a shortening of fatty acids was observed upon ablation of unsaturated fatty acid synthesis (Pineau et al , 2008). Overexpression of Sct1p was found to decrease the average cellular fatty acid length, suggesting that Sct1p also competes for substrate with the fatty acid elongases that use C16:0-CoA as substrate, although it must be noted that the role of the fatty acid elongases in the synthesis of C18:0-CoA is not fully established (Rossler et al , 2003). According to the proposed mechanism, the substrate preferences and the activities of Sct1p, Ole1p, and the fatty acid elongases determine the cellular fatty acid composition (Figure 7).…”

Section: Discussionmentioning

confidence: 99%

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The yeast acyltransferase Sct1p regulates fatty acid desaturation by competing with the desaturase Ole1p

Smet

Vittone

Scherer

et al. 2012

MBoC

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The degree of fatty acid unsaturation, that is, the ratio of unsaturated versus saturated fatty acyl chains, determines membrane fluidity. Regulation of expression of the fatty acid desaturase Ole1p was hitherto the only known mechanism governing the degree of fatty acid unsaturation in Saccharomyces cerevisiae. We report a novel mechanism for the regulation of fatty acid desaturation that is based on competition between Ole1p and the glycerol-3-phosphate acyltransferase Sct1p/Gat2p for the common substrate C16:0-CoA. Deletion of SCT1 decreases the content of saturated fatty acids, whereas overexpression of SCT1 dramatically decreases the desaturation of fatty acids and affects phospholipid composition. Whereas overexpression of Ole1p increases desaturation, co-overexpression of Ole1p and Sct1p results in a fatty acid composition intermediate between those obtained upon overexpression of the enzymes separately. On the basis of these results, we propose that Sct1p sequesters C16:0-CoA into lipids, thereby shielding it from desaturation by Ole1p. Taking advantage of the growth defect conferred by overexpressing SCT1, we identified the acyltransferase Cst26p/Psi1p as a regulator of Sct1p activity by affecting the phosphorylation state and overexpression level of Sct1p. The level of Sct1p phosphorylation is increased when cells are supplemented with saturated fatty acids, demonstrating the physiological relevance of our findings.

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Section: Discussionmentioning

confidence: 99%

“…The endoplasmic reticulum (ER)–based fatty acid elongases Elo1p, Elo2p, and Elo3p can elongate the acyl-CoA's up to C26. Although essential, the very long acyl chains are very low in abundance (Rossler et al , 2003). …”

Section: Introductionmentioning

confidence: 99%

The yeast acyltransferase Sct1p regulates fatty acid desaturation by competing with the desaturase Ole1p

Smet

Vittone

Scherer

et al. 2012

MBoC

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“…16, 19 These long-chain fatty acids are synthesized by an elongation system 19–21 whose components have now been identified and this has led to a model for how the length of the fatty acid is determined. 22 The functions of such a long-chain fatty in sphingolipids are not well defined, although it may have something to do with the fact that they span both leaflets of a membrane bilayer.…”

Section: Sphingolipid Metabolism In S Cerevisiaementioning

confidence: 99%

Roles for Sphingolipids in Saccharomyces cerevisiae

Dickson

2010

Advances in Experimental Medicine and Biology

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Studies using Saccharomyces cerevisiae, the common baker's or brewer's yeast, have progressed over the past twenty years from knowing which sphingolipids are present in cells and a basic outline of how they are made to a complete or nearly complete directory of the genes that catalyze their anabolism and catabolism. In addition, cellular processes that depend upon sphingolipids have been identified including protein trafficking/exocytosis, endocytosis and actin cytoskeleton dynamics, membrane microdomains, calcium signaling, regulation of transcription and translation, cell cycle control, stress resistance, nutrient uptake and aging. These will be summarized here along with new data not previously reviewed. Advances in our knowledge of sphingolipids and their roles in yeast are impressive but molecular mechanisms remain elusive and are a primary challenge for further progress in understanding the specific functions of sphingolipids.

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“…The duplicated pair FEN1 and ELO1 may represent a situation in which both proteins have specialized to function with a subset of substrates (Rossler et al , 2003). FEN1 synthesizes longer fatty acids and ELO1 synthesizes shorter fatty acids.…”

Section: Resultsmentioning

confidence: 99%

In silicoevidence for functional specialization after genome duplication in yeast

Turunen

Seelke

Macosko

2009

FEMS Yeast Research

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A fairly recent whole-genome duplication (WGD) event in yeast enables the effects of gene duplication and subsequent functional divergence to be characterized. We examined 15 ohnolog pairs (i.e. paralogs from a WGD) out of c. 500 Saccharomyces cerevisiae ohnolog pairs that have persisted over an estimated 100 million years of evolution. These 15 pairs were chosen for their high levels of asymmetry, i.e. within the pair, one ohnolog had evolved much faster than the other. Sequence comparisons of the 15 pairs revealed that the faster evolving duplicated genes typically appear to have experienced partially – but not fully – relaxed negative selection as evidenced by an average nonsynonymous/synonymous substitution ratio (dN/dSavg=0.44) that is higher than the slow-evolving genes' ratio (dN/dSavg=0.14) but still <1. Increased number of insertions and deletions in the fast-evolving genes also indicated loosened structural constraints. Sequence and structural comparisons indicated that a subset of these pairs had significant differences in their catalytically important residues and active or cofactor-binding sites. A literature survey revealed that several of the fast-evolving genes have gained a specialized function. Our results indicate that subfunctionalization and even neofunctionalization has occurred along with degenerative evolution, in which unneeded functions were destroyed by mutations.

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Functional differentiation and selective inactivation of multiple Saccharomyces cerevisiae genes involved in very-long-chain fatty acid synthesis

Cited by 61 publications

References 26 publications

The yeast acyltransferase Sct1p regulates fatty acid desaturation by competing with the desaturase Ole1p

The yeast acyltransferase Sct1p regulates fatty acid desaturation by competing with the desaturase Ole1p

Roles for Sphingolipids in Saccharomyces cerevisiae

In silicoevidence for functional specialization after genome duplication in yeast

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