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Energetic Mitochondrial Function in Yeast Phase of Pathogenic Fungus Paracoccidioides brasiliensis
Martins, V.P.a,#; Soriani, F.M.a; Magnani, T.a; Tudella, V.G.a; Goldman, G.H.b; Curti, C.c and Uyemura, S.A.a
From: aDepartamento de Análises Clínicas, Toxicológicas e Bromatológicas, bDepartamento de Ciências Farmacêuticas and cDepartamento de Física e Química. Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo.
#Address correspondence to: Vicente P. Martins, Dep Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo. Av. Café, s/n, Ribeirão Preto, SP, 14040-903, Brazil.Tel: 0055 16 3602-4171; Fax:0055 16 3602-4725; E-Mail: vmartins@fcfrp.usp.br
This study was addressed in order to identify differences between the respiratory chain of mammalian host and the fungus Paracoccidioides brasiliensis, planning to use them as a pharmacological target. Respiration, membrane potential and oxidative phosphorylation of mitochondria of Paracoccidioides brasiliensis spheroplasts were evaluated in situ. A functional respiratory chain was demonstrated. Adenosine 5'-diphosphate (ADP) induced a transition from resting to phosphorylating respiration in succinate-energized mitochondria. The ability of the fungus to oxidize exogenous NADH, together with the insensitivity of its cocktail substrate-supported respiration to rotenone, and sensitivity to flavone, indicates the presence of an alternative NADH-ubiquinone oxidoreductase. In addition, the malate/NAD+-supported respiration suggests that the glyoxylate pathway contributes for a NADH and succinate production. The partial sensitivity of NADH/succinate-supported respiration to antimycin A and cyanide, together with its sensitivity to benzohydroxamic acid, indicates the presence of an alternative oxidase. Moreover, the non-oxidation of traditional complex I substrates indicates, in yeast phase, an absence of functional complex I.
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