title: The adaptive metabolic response involves specific protein glutathionylation during the filamentation process in the pathogen Candida albicans.
abstract: Candida albicans is an opportunist pathogen responsible for a large spectrum of infections, from superficial mycosis to the systemic disease candidiasis. Its ability to adopt various morphological forms, such as unicellular yeasts, filamentous pseudohyphae and hyphae, contributes to its ability to survive within the host. It has been suggested that the antioxidant glutathione is involved in the filamentation process. We investigated S-glutathionylation, the reversible binding of glutathione to proteins, and the functional consequences on C. albicans metabolic remodeling during the yeast-to-hyphae transition. Our work provided evidence for the specific glutathionylation of mitochondrial proteins involved in bioenergetics pathways in filamentous forms and a regulation of the main enzyme of the glyoxylate cycle, isocitrate lyase, by glutathionylation. Isocitrate lyase inactivation in the hyphal forms was reversed by glutaredoxin treatment, in agreement with a glutathionylation process, which was confirmed by proteomic data showing the binding of one glutathione molecule to the enzyme (data are available via ProteomeXchange with identifier PXD003685). We also assessed the effect of alternative carbon sources on glutathione levels and isocitrate lyase activity. Changes in nutrient availability led to morphological flexibility and were related to perturbations in glutathione levels and isocitrate lyase activity, confirming the key role of the maintenance of intracellular redox status in the adaptive metabolic strategy of the pathogen.
authors.affiliation: Laboratoire Mitochondries, Métaux et Stress Oxydant, Institut Jacques Monod, UMR 7592, Université Paris-Diderot/CNRS, 15 rue Hélène Brion, 75013 Paris, France.
authors.forename: R
authors.initials: R
authors.lastname: Gergondey
authors.affiliation: Plateforme Protéomique structurale et fonctionnelle/Spectrométrie de masse, Institut Jacques Monod, UMR 7592, Université Paris-Diderot/CNRS, 15 rue Hélène Brion, 75013 Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Garcia
authors.affiliation: Laboratoire Mitochondries, Métaux et Stress Oxydant, Institut Jacques Monod, UMR 7592, Université Paris-Diderot/CNRS, 15 rue Hélène Brion, 75013 Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: Serre
authors.affiliation: Laboratoire Mitochondries, Métaux et Stress Oxydant, Institut Jacques Monod, UMR 7592, Université Paris-Diderot/CNRS, 15 rue Hélène Brion, 75013 Paris, France.
authors.forename: J M
authors.initials: JM
authors.lastname: Camadro
authors.affiliation: Laboratoire Mitochondries, Métaux et Stress Oxydant, Institut Jacques Monod, UMR 7592, Université Paris-Diderot/CNRS, 15 rue Hélène Brion, 75013 Paris, France. Electronic address: francoise.auchere@ijm.fr.
authors.forename: F
authors.initials: F
authors.lastname: Auchère
mesh_terms: D000154:Aconitate Hydratase / Q000032:analysis / Q000378:metabolism; D000595:Amino Acid Sequence; D002176:Candida albicans / Q000737:chemistry / Q000201:enzymology / Q000254:growth & development* / Q000378:metabolism; D002177:Candidiasis / Q000382:microbiology*; D005656:Fungal Proteins / Q000032:analysis / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D025301:Hyphae / Q000737:chemistry / Q000201:enzymology / Q000254:growth & development* / Q000378:metabolism; D007522:Isocitrate Lyase / Q000032:analysis / Q000378:metabolism; D008292:Malate Synthase / Q000032:analysis / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000032:analysis / Q000378:metabolism*; D008958:Models, Molecular; D016415:Sequence Alignment
chemical_list: D005656:Fungal Proteins; D024101:Mitochondrial Proteins; D008292:Malate Synthase; D007522:Isocitrate Lyase; D000154:Aconitate Hydratase; D005978:Glutathione
keywords: Candida albicans; Filamentation; Glutathionylation; Isocitrate lyase; Mitochondria