Intracellular Acetyl Unit Transport in Fungal Carbon Metabolism

Overview

Journal Eukaryot Cell

Publisher American Society for Microbiology

Specialty Molecular Biology

Date 2010 Oct 5

PMID 20889721

Citations 67

Authors

Karin Strijbis

Ben Distel

Affiliations

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Abstract

Acetyl coenzyme A (acetyl-CoA) is a central metabolite in carbon and energy metabolism. Because of its amphiphilic nature and bulkiness, acetyl-CoA cannot readily traverse biological membranes. In fungi, two systems for acetyl unit transport have been identified: a shuttle dependent on the carrier carnitine and a (peroxisomal) citrate synthase-dependent pathway. In the carnitine-dependent pathway, carnitine acetyltransferases exchange the CoA group of acetyl-CoA for carnitine, thereby forming acetyl-carnitine, which can be transported between subcellular compartments. Citrate synthase catalyzes the condensation of oxaloacetate and acetyl-CoA to form citrate that can be transported over the membrane. Since essential metabolic pathways such as fatty acid β-oxidation, the tricarboxylic acid (TCA) cycle, and the glyoxylate cycle are physically separated into different organelles, shuttling of acetyl units is essential for growth of fungal species on various carbon sources such as fatty acids, ethanol, acetate, or citrate. In this review we summarize the current knowledge on the different systems of acetyl transport that are operational during alternative carbon metabolism, with special focus on two fungal species: Saccharomyces cerevisiae and Candida albicans.

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References

Strijbis K, van Roermund C, Hardy G, van den Burg J, Bloem K, de Haan J . Identification and characterization of a complete carnitine biosynthesis pathway in Candida albicans. FASEB J. 2009; 23(8):2349-59. DOI: 10.1096/fj.08-127985. View

Fradin C, Kretschmar M, Nichterlein T, Gaillardin C, dEnfert C, Hube B . Stage-specific gene expression of Candida albicans in human blood. Mol Microbiol. 2003; 47(6):1523-43. DOI: 10.1046/j.1365-2958.2003.03396.x. View

Hedges D, Proft M, Entian K . CAT8, a new zinc cluster-encoding gene necessary for derepression of gluconeogenic enzymes in the yeast Saccharomyces cerevisiae. Mol Cell Biol. 1995; 15(4):1915-22. PMC: 230417. DOI: 10.1128/MCB.15.4.1915. View

Odds F . Candida infections: an overview. Crit Rev Microbiol. 1987; 15(1):1-5. DOI: 10.3109/10408418709104444. View

Kunze M, Pracharoenwattana I, Smith S, Hartig A . A central role for the peroxisomal membrane in glyoxylate cycle function. Biochim Biophys Acta. 2006; 1763(12):1441-52. DOI: 10.1016/j.bbamcr.2006.09.009. View

Strijbis K, van Roermund C, van den Burg J, van den Berg M, Hardy G, Wanders R . Contributions of carnitine acetyltransferases to intracellular acetyl unit transport in Candida albicans. J Biol Chem. 2010; 285(32):24335-46. PMC: 2915669. DOI: 10.1074/jbc.M109.094250. View

van Roermund C, Hettema E, van den Berg M, Tabak H, Wanders R . Molecular characterization of carnitine-dependent transport of acetyl-CoA from peroxisomes to mitochondria in Saccharomyces cerevisiae and identification of a plasma membrane carnitine transporter, Agp2p. EMBO J. 1999; 18(21):5843-52. PMC: 1171650. DOI: 10.1093/emboj/18.21.5843. View

Palmieri L, Lasorsa F, Iacobazzi V, Runswick M, Palmieri F, Walker J . Identification of the mitochondrial carnitine carrier in Saccharomyces cerevisiae. FEBS Lett. 2000; 462(3):472-6. DOI: 10.1016/s0014-5793(99)01555-0. View

Kunze M, Kragler F, Binder M, Hartig A, Gurvitz A . Targeting of malate synthase 1 to the peroxisomes of Saccharomyces cerevisiae cells depends on growth on oleic acid medium. Eur J Biochem. 2002; 269(3):915-22. DOI: 10.1046/j.0014-2956.2001.02727.x. View

10.

IJlst L, van Roermund C, Iacobazzi V, Oostheim W, Ruiter J, Williams J . Functional analysis of mutant human carnitine acylcarnitine translocases in yeast. Biochem Biophys Res Commun. 2001; 280(3):700-6. DOI: 10.1006/bbrc.2000.4178. View

11.

White S, Rosenbach A, Lephart P, Nguyen D, Benjamin A, Tzipori S . Self-regulation of Candida albicans population size during GI colonization. PLoS Pathog. 2007; 3(12):e184. PMC: 2134954. DOI: 10.1371/journal.ppat.0030184. View

12.

Carman A, Vylkova S, Lorenz M . Role of acetyl coenzyme A synthesis and breakdown in alternative carbon source utilization in Candida albicans. Eukaryot Cell. 2008; 7(10):1733-41. PMC: 2568070. DOI: 10.1128/EC.00253-08. View

13.

van Roermund C, Elgersma Y, Singh N, Wanders R, Tabak H . The membrane of peroxisomes in Saccharomyces cerevisiae is impermeable to NAD(H) and acetyl-CoA under in vivo conditions. EMBO J. 1995; 14(14):3480-6. PMC: 394415. DOI: 10.1002/j.1460-2075.1995.tb07354.x. View

14.

Zhou H, Lorenz M . Carnitine acetyltransferases are required for growth on non-fermentable carbon sources but not for pathogenesis in Candida albicans. Microbiology (Reading). 2008; 154(Pt 2):500-509. DOI: 10.1099/mic.0.2007/014555-0. View

15.

Strijbis K, van Roermund C, Visser W, Mol E, van den Burg J, MacCallum D . Carnitine-dependent transport of acetyl coenzyme A in Candida albicans is essential for growth on nonfermentable carbon sources and contributes to biofilm formation. Eukaryot Cell. 2008; 7(4):610-8. PMC: 2292619. DOI: 10.1128/EC.00017-08. View

16.

Fradin C, de Groot P, MacCallum D, Schaller M, Klis F, Odds F . Granulocytes govern the transcriptional response, morphology and proliferation of Candida albicans in human blood. Mol Microbiol. 2005; 56(2):397-415. DOI: 10.1111/j.1365-2958.2005.04557.x. View

17.

van den Berg M, Steensma H . ACS2, a Saccharomyces cerevisiae gene encoding acetyl-coenzyme A synthetase, essential for growth on glucose. Eur J Biochem. 1995; 231(3):704-13. DOI: 10.1111/j.1432-1033.1995.tb20751.x. View

18.

Lorenz M, Bender J, Fink G . Transcriptional response of Candida albicans upon internalization by macrophages. Eukaryot Cell. 2004; 3(5):1076-87. PMC: 522606. DOI: 10.1128/EC.3.5.1076-1087.2004. View

19.

Pracharoenwattana I, Cornah J, Smith S . Arabidopsis peroxisomal citrate synthase is required for fatty acid respiration and seed germination. Plant Cell. 2005; 17(7):2037-48. PMC: 1167550. DOI: 10.1105/tpc.105.031856. View

20.

Rottensteiner H, Theodoulou F . The ins and outs of peroxisomes: co-ordination of membrane transport and peroxisomal metabolism. Biochim Biophys Acta. 2006; 1763(12):1527-40. DOI: 10.1016/j.bbamcr.2006.08.012. View