Mitochondrial drug targets in apicomplexan parasites.
In evolutionary terms, mitochondria in apicomplexan parasites appear to be "relicts-in-the-making": they possess the smallest mitochondrial genomes known, encoding only three proteins, and in one genus, Cryptosporidium, the genome is eliminated altogether. Several features of mitochondrial physiology provide validated or potential targets for antiparasitic drugs. Atovaquone, a broad spectrum antiparasitic drug, selectively inhibits mitochondrial electron transport at the cytochrome bc(1) complex and collapses mitochondrial membrane potential. Recent investigations using model systems provide important insights into the mechanism of action for this drug, which may prove valuable for development of other selective inhibitors of mitochondrial electron transport. Although mitochondria do not appear to be a source of ATP during the erythrocytic stages in Plasmodium species, they do serve other critical functions, including the assembly of iron-sulfur clusters and various other biosynthetic processes depending on the species. To serve these metabolic functions, parasites need to maintain the apparatus for mitochondrial genome replication, repair, recombination, transcription, and translation, components of which are encoded in the nucleus and imported into the mitochondrion. Several unusual aspects of the components of this apparatus are coming to light through genome sequence analyses, and could provide potential targets for antiparasitic drug discovery and development.
Mather
Michael W
MW
Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, Pennsylvania 19129, USA.
Henry
Karl W
KW
Vaidya
Akhil B
AB
D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage; D016782:Apicomplexa / Q000187:drug effects* / Q000235:genetics / Q000469:parasitology*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000235:genetics
D000981:Antiprotozoal Agents