Figure 2.

Metabolic pathways for fatty acid and acetate utilization. Triacylglycerides, which accumulate inside of lipid droplets, are converted to fatty acids and transferred to peroxisomes for catabolism. Fatty acids are converted to acetyl-coenzyme A (-CoA) by the fatty acid β-oxidation pathway. In ascomycete yeasts like Saccharomyces cerevisiae, the β-oxidation pathway is exclusively peroxisomal (Hiltunen et al., 2003; Shen and Burger, 2009). However, in most other fungi, this pathway occurs in peroxisomes and mitochondria (Maggio-Hall and Keller, 2004; Boisnard et al., 2009; Shen and Burger, 2009; Kretschmer et al., 2012a,b; Patkar et al., 2012) (only the peroxisomal pathway is illustrated). The anaplerotic glyoxylate cycle then allows the conversion of acetyl-CoA to four-carbon dicarboxylic acids by bypassing the decarboxylation reactions of the tricarboxylic acid (TCA) cycle (note that two reactions can feed acetyl-CoA into the glyoxylate cycle, asterisks). The glyoxylate shunt intermediates can replenish the TCA cycle or serve as precursors for gluconeogenesis (shuttling between compartments of some intermediates, such as malate and oxaloacetate, is not illustrated). The glyoxylate cycle consists of five enzymatic reactions, of which three are shared with the TCA cycle. Depending on the fungal lineage, these three enzymatic steps (blue font) can take place in peroxisomes, mitochondria or the cytosol (except for citrate synthase, for which no cytosolic form has been described so far). In contrast, the specific enzymes of the glyoxylate cycle, isocitrate lyase and malate synthase (red font), are typically peroxisomal (Kunze et al., 2006; Hynes, 2010; Strijbis and Distel, 2010). The most notable exception is S. cerevisiae, which harbors cytosolic isocitrate lyase (Taylor et al., 1996). Peroxisomal β-oxidation-produced acetyl-CoA can also be transferred to mitochondria for energy generation via TCA cycle. This transport depends on the interconversion of acetyl-CoA and acetyl-carnitine by carnitine acetyl-CoA transferases (green font). Acetyl-carnitine can then be imported into mitochondria by an acyl-carnitine carrier protein (Strijbis and Distel, 2010). Fatty acyl-CoA β-oxidation intermediates may also be transferred to mitochondria for further β-oxidation and acetyl-CoA generation within mitochondria (not shown). Cytosolic acetyl-CoA, which can be produced from C2 compounds, can also be transferred via acetyl-carnitine to mitochondria and peroxisomes for metabolism via the TCA and glyoxylate cycles. Only relevant enzymes are shown, abbreviations are as follows: ACO, aconitase; CAT, carnitine acetyltransferase; CS, citrate synthase; FUM, fumarase; IDH, isocitrate dehydrogenase; IL, isocitrate lyase; KDH, α-ketoglutarate dehydrogenase; MDH, malate dehydrogenase; MS, malate synthase; SCS, succinyl CoA synthetase; SDH, succinate dehydrogenase.