Respiratory inhibition of isolated mammalian mitochondria by salivary antifungal peptide histatin-5.
Histatin-5 is a peptide secreted in the human saliva, which possesses powerful antifungal activity. Previous studies have shown that this peptide exerts its candidacidal activity, through the inhibition of both mitochondrial respiration and the formation of reactive oxygen species. The purpose of the present study was to investigate the biological consequences of histatin-5 action on mammalian mitochondria to verify if the toxic mechanism exerted on mitochondria from Candida albicans is an exclusive for fungal cells. Moreover, hypothesising that the damage exerted on mitochondria may induce programmed cellular death pathways, we evaluated two main markers of apoptosis: the mitochondrial membrane potential (DeltaPsi) and the release of cytochrome c. The results obtained show that exposure of isolated mammalian mitochondria to histatin-5 determines: (i) a large inhibition of the respiratory chain at the level of complex I, (ii) a slight decrease in the mitochondrial membrane potential, and (iii) no release of cytochrome c.
Petruzzelli
R
R
Department of Biomedical Sciences, University G. D'Annunzio Via dei Vestini, 31, 66100, Chieti Scalo (CH), Italy. r.petruzzelli@dsb.unich.it
Clementi
M E
ME
Marini
S
S
Coletta
M
M
Di Stasio
E
E
Giardina
B
B
Misiti
F
F
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D019069:Cell Respiration / Q000187:drug effects* / Q000502:physiology*; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D054808:Histatins; D008564:Membrane Potentials / Q000187:drug effects* / Q000502:physiology*; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012471:Salivary Proteins and Peptides / Q000494:pharmacology*
D000935:Antifungal Agents; C068075:HTN3 protein, human; D054808:Histatins; D012471:Salivary Proteins and Peptides; D045304:Cytochromes c