Classical and alternative components of the mitochondrial respiratory chain in pathogenic fungi as potential therapeutic targets Vicente de Paulo Martins & Taisa Magnani Dinamarco & Carlos Curti & Sérgio Akira Uyemura Published online: 27 January 2011 # Springer Science+Business Media, LLC 2011 Abstract The frequency of opportunistic fungal infection has increased drastically, mainly in patients who are immuno- compromised due to organ transplant, leukemia or HIV infection. In spite of this, only a few classes of drugs with a limited array of targets, are available for antifungal therapy. Therefore, more specific and less toxic drugs with new molecular targets is desirable for the treatment of fungal infections. In this context, searching for differences between mitochondrial mammalian hosts and fungi in the classical and alternative components of the mitochondrial respiratory chain may provide new potential therapeutic targets for this purpose. Keywords Fungal Mitochondria . Fungal infection . Therapeutic targets . Antifungal Introduction Fungi represent a group of eukaryotic organisms that are well adapted to a diversity of environments. Fungi are important for the recycling of carbon and nitrogen, food, enzymes, and biodetergents, as well as for antibiotic production. On the other hand, fungi can be dangerous contaminants of grains and seeds because of their potential for mycotoxin production, and fungi are responsible for several animal and plant diseases. In the past few decades, the frequency of opportunistic fungal infection has increased drastically, mainly in patients who are immunocompromised due to organ transplant, leukemia or HIV infection (Walsh and Groll 1999; Groll and Walsh 2001; Brakhage and Liebmann 2005). Candida spp. and Aspergillus spp. remain the most frequent causes of invasive fungal infection (Richardson and Lass-Flörl 2008). Furthermore, Crypto- coccus neoformans is the most common cause of menin- goencephalitis in HIV-infected patients (Groll and Walsh 2001). Other fungi and yeast, such as Fusarium spp., Zygomyces, Trichosporon and Coccidioides immitis, have also emerged as opportunistic fungi in immunocompro- mised patients (Shao et al. 2007). In spite of the increase in fungal infections, only a few classes of drugs (with a limited array of targets) are available for antifungal therapy; these drugs include polyenes, azoles, allylamines, nucleoside analogs and the recently introduced echinocandins. For many years, ampho- tericin B was considered the “gold standard” treatment for invasive fungal infection (Petrikkos and Skiada 2007). However, this drug presents undesirable side effects including fever, nausea, vomiting and nephrotoxicity (Bates et al. 2001). Therefore, many of these classes of drugs have limited use, making the discovery of new, more specific and less toxic drugs with new molecular targets desirable for the treatment of invasive fungal infections. Along those lines, mitochondria are potential targets, because they are present in most eukaryotic cells. In addition to being responsible for more than 90% of cellular ATP production, these organelles play several roles, including generation and regulation of reactive oxygen species, calcium homeostasis, programmed cell death and metabolic processes (involving V. P. Martins : T. M. Dinamarco : S. A. Uyemura (*) Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. Café, s/n, 14040-903 Ribeirão Preto, SP, Brazil e-mail: suyemura@fcfrp.usp.br C. Curti Departamento de Física e Química. Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. Café, s/n, 14040-903 Ribeirão Preto, SP, Brazil J Bioenerg Biomembr (2011) 43:81–88 DOI 10.1007/s10863-011-9331-1