Mitochondrial function in the yeast form of the pathogenic fungus Paracoccidioides brasiliensis

Autor(es)

Martins, Vicente P. ^[1] ; Soriani, Frederico M. ^[1] ; Magnani, Taisa ^[1] ; Tudella, Valaria G. ^[1] ; Goldman, Gustavo H. ^[2] ; Curti, Carlos ^[3] ; Uyemura, Sergio A. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Anal Clin Toxicol & Bromatol, BR-14040903 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Ciencias Farmaceut, BR-14040903 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Quim & Fis, BR-14040903 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Bioenergetics and Biomembranes; v. 40, n. 4, p. 297-305, AUG 2008.
• Citações Web of Science: 9

Resumo

Differences between the respiratory chain of the fungus Paracoccidioides brasiliensis and its mammalian host are reported. Respiration, membrane potential, and oxidative phosphorylation in mitochondria from P. brasiliensis spheroplasts were evaluated in situ, and the presence of a complete (Complex I-V) functional respiratory chain was demonstrated. In succinate-energized mitochondria, ADP induced a transition from resting to phosphorylating respiration. The presence of an alternative NADH-ubiquinone oxidoreductase was indicated by: (i) the ability to oxidize exogenous NADH and (ii) the lack of sensitivity to rotenone and presence of sensitivity to flavone. Malate/NAD(+)-supported respiration suggested the presence of either a mitochondrial pyridine transporter or a glyoxylate pathway contributing to NADH and/or succinate production. Partial sensitivity of NADH/succinate-supported respiration to antimycin A and cyanide, as well as sensitivity to benzohydroxamic acids, suggested the presence of an alternative oxidase in the yeast form of the fungus. An increase in activity and gene expression of the alternative NADH dehydrogenase throughout the yeast's exponential growth phase was observed. This increase was coupled with a decrease in Complex I activity and gene expression of its subunit 6. These results support the existence of alternative respiratory chain pathways in addition to Complex I, as well as the utilization of NADH-linked substrates by P. brasiliensis. These specific components of the respiratory chain could be useful for further research and development of pharmacological agents against the fungus. (AU)

• Processo FAPESP: 99/04126-0 - Estudos moleculares bioenergéticos e regulação intracelular de cálcio no fungo sistêmico Paracoccidioides brasiliensis
• Beneficiário: Sergio Akira Uyemura
• Modalidade de apoio: Auxílio à Pesquisa - Regular