Intracellular Acetyl Unit Transport in Fungal Carbon Metabolism

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 ␤-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.

Mitochondrial Carnitine-Dependent Acetyl Coenzyme A Transport Is Required for Normal Sexual and Asexual Development of the Ascomycete Gibberella zeae

“…Mutations in CAT2 homologs in other fungi did not trigger phenotypic changes in development, except in utilization of nonfermentable carbon sources such as acetate and ethanol (56,57). However, in this study, the G. zeae CAT2 deletion mutant was also deficient in spore germination and long-chain fatty acid utilization (Table 1 and Fig.…”

“…9). CAT2 of G. zeae localized to both peroxisomes and the cytosol, but CAT2 homologs of other fungi are known to function only in the cytosol (56,57). Moreover, CAT2 localized exclusively to the cytosol in acetate medium, as acetyl-CoA produced from acetate by ACS1 (Fig.…”

“…In fungi, acetyl-CoA is produced in peroxisomes via peroxisomal ␤-oxidation (22,28), in the mitochondria via the mitochondrion-associated pyruvate dehydrogenase complex or mitochondrial ␤-oxidation (37), and in the nuclei and cytosol by ACL and ACSs (32,33,52,57,60). Moreover, eukaryotic cells have an efficient shuttle system that allows acetyl-CoA to be transported between the cytosol and organelles via a process mediated by carnitine acetyltransferases (CATs) (27).…”

The methylaspartate cycle in haloarchaea and its possible role in carbon metabolism

“…Therefore, the functioning of isocitrate lyase in the presence of isocitrate dehydrogenase requires a large pool of isocitrate, overproduction of isocitrate lyase, or complicated regulation mechanisms controlling isocitrate dehydrogenase activity like, for example, phosphorylation in enterobacteria (El-Mansi et al, 1994;Cozzone and El-Mansi, 2005). Alternatives are synthesis of different isoforms of isocitrate dehydrogenase with different kinetic constants, depending on conditions (Reeves et al, 1983(Reeves et al, , 1986Banerjee et al, 2005), or eukaryotic-specific mechanism of spatial separation of the glyoxylate and tricarboxylic acid cycles, like it happens in glyoxysomes of fungi and plants (Graham, 2008;Strijbis and Distel, 2010). However, these mechanisms are not functional in haloarchaea, and accumulation of large amount of isocitrate or isocitrate lyase is possible only in actively growing culture.…”

Functional Analyses of Two Acetyl Coenzyme A Synthetases in the Ascomycete Gibberella zeae

“…Citrate that is exported from the TCA cycle in mitochondria through tricarboxylate carriers is cleaved into oxaloacetate and cytosolic acetyl-CoA by ACL. In the case of Saccharomyces cerevisiae and Candida albicans, however, cytosolic acetyl-CoA is synthesized through the pyruvate-acetaldehyde-acetate pathway, which is mediated by acetyl-CoA synthetases (ACSs) (10,17,60,61,63,66). ACSs are conserved in most eukaryotes and are thought to evolve from a mitochondrial origin (34).…”