Back to the Future: Candida Mitochondria and Energetics

This chapter reviews the role of mitochondria in human fungal pathogens, focusing upon Candida albicans, Candida glabrata, and Candida parapsilosis. The respiratory pathways of Candida species are highlighted along with the roles of mitochondria in morphogenesis, adaptive responses to oxidant stress and carbon depletion, and antifungal drug resistance and sensitivity. The focus therefore is on the role of mitochondria in the pathogenesis of candidiasis and developing the concept that there are differences in mitochondria of mammalian cells versus pathogens. The study of mitochondria in Candida species first followed those that were of industrial importance, examples being Candida utilis and Candida lipolytica. The morphogenesis of C. albicans has long been featured as critical to the establishment of candidiasis. Mitochondria play an active role in detoxifying reactive oxidant species (ROS) produced during cell metabolism. This has been convincingly shown through the use of inhibitors of respiratory complexes. 7-Chlorotetrazolo[5,1-c]benzo[1,2,4]triazine (CTBT) increases the activity of several antimycotics, including flucytosine as well as azoles. The target of histatin 5, a human basic salivary peptide that has demonstrated antifungal activity, was initially shown to be the energized mitochondria. There is ample proof that mitochondrial functions as well as regulation of these functions vary among pathogenic and model fungi, and that mammalian mitochondria have less complexity with regard to respiratory pathways.