Carnitine and carnitine acetyltransferases in the yeast Saccharomyces cerevisiae: a role for carnitine in stress protection
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To date, the only reported metabolic and physiological roles for carnitine in Saccharomyces cerevisiae are related to the activity of the carnitine shuttle. In yeast, the shuttle transfers peroxisomal activated acetyl-residues to the mitochondria. However, acetyl-CoA can also be metabolised by the glyoxylate cycle to form succinate. The two pathways, therefore, provide a metabolic bypass for each other, and carnitine-dependent phenotypes have only been described in strains with non-functional peroxisomal citrate synthase, Cit2p. Here, we present evidence for a role of carnitine in stress protection that is independent of CIT2 and of the carnitine shuttle. Data show that carnitine improves growth during oxidative stress and in the presence of weak organic acids in wt and in CAT deletion strains. Our data also show that strains with single, double and triple deletions of the three CAT genes generally present identical phenotypes, but that the deletion of CAT2 decreases survival during oxidative stress in a carnitine-independent manner. Overexpression of single CAT genes does not lead to cross-complementation, suggesting a highly specific metabolic role for each enzyme. The data suggest that carnitine protects cells from oxidative and organic acid stress, while CAT2 contributes to the response to oxidative stress.
KeywordsYeast Carnitine Carnitine acetyltransferase Cellular stress Glyoxylate cycle
This work was supported by the South African Medical Research Council, the National Research Foundation of South Africa, and Winetech.
- Ausubel FM, Brent R, Kingston RE, Moore DD, Seidman JG (1994) Current protocols in molecular biology. Wiley, New YorkGoogle Scholar
- Kawahata M, Masaki K, Fujii T, lefuji H (2006) Yeast genes involved in response to lactic and acetic: acidic conditions caused by the organic acids in Saccharomyces cerevisiae cultures induce expression of intracellular metal metabolism genes regulated by Aft1p. FEMS Yeast Res 6:924–936PubMedCrossRefGoogle Scholar
- Sambrook J, Fritsch EF, Maniatis T (1989) Molecular cloning: a laboratory manual, 2nd edn. Cold Spring Harbor Laboratory Press, Cold Spring HarborGoogle Scholar