The activity of the glyoxylate cycle in peroxisomes of Candida albicans depends on a functional beta-oxidation pathway: evidence for reduced metabolite transport across the peroxisomal membrane

Katarzyna Piekarska, Guy Hardy, Els Mol, Janny van den Burg, Karin Strijbis, Carlo van Roermund, Marlene van den Berg, Ben Distel

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The glyoxylate cycle, a metabolic pathway required for generating C-4 units from C-2 compounds, is an important factor in virulence, in both animal and plant pathogens. Here, we report the localization of the key enzymes of this cycle, isocitrate lyase (Icl1; EC and malate synthase (Mls1; EC, in the human fungal pathogen Candida albicans. Immunocytochemistry in combination with subcellular fractionation showed that both Icl1 and Mls1 are localized to peroxisomes, independent of the carbon source used. Although Icl1 and Mls1 lack a consensus type I peroxisomal targeting signal (PTS1), their import into peroxisomes was dependent on the PTS1 receptor Pex5p, suggesting the presence of non-canonical targeting signals in both proteins. Peroxisomal compartmentalization of the glyoxylate cycle is not essential for proper functioning of this metabolic pathway because a pex5 Delta/Delta strain, in which Icl1 and Mls1 were localized to the cytosol, grew equally as well as the wild-type strain on acetate and ethanol. Previously, we reported that a fox2 Delta/Delta strain that is completely deficient in fatty acid beta-oxidation, but has no peroxisomal protein import defect, displayed strongly reduced growth on non-fermentable carbon sources such as acetate and ethanol. Here, we show that growth of the fox2 Delta/Delta strain on these carbon compounds can be restored when Icl1 and Mls1 are relocated to the cytosol by deleting the PEX5 gene. We hypothesize that the fox2 Delta/Delta strain is disturbed in the transport of glyoxylate cycle products and/or acetyl-CoA across the peroxisomal membrane and discuss the possible relationship between such a transport defect and the presence of giant peroxisomes in the fox2 Delta/Delta mutant
Original languageEnglish
Pages (from-to)3061-3072
JournalMicrobiology (Reading, England)
Issue numberPart 10
Publication statusPublished - 2008

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