Mitochondrial and plastid functions as antimalarial drug targets.
Malaria parasites possess three genomes: the nuclear chromosomes, the mitochondrial genome, and the plastid genome. Realization that the parasites contain a plastid remnant with its own genome has created much excitement not only from a basic biological point of view but also from the prospects for developing new antimalarial drugs. Both the mitochondrial and the plastid genomes are the smallest examples of their kind known to date. The plastid appears to be derived from an ancestral secondary endosymbiotic event. Interestingly, the main functions usually associated with a mitochondrion and a plastid, i.e. oxidative phosphorylation and photosynthesis, do not appear to be conserved in malaria parasites. Completion of the parasite genome sequence has provided the opportunity to assess functions assigned to these highly derivatized organelles. It is clear that these organelles serve vital functions since interference with their activity is incompatible with parasite growth. A number of antimalarial compounds target functions of either the mitochondrion or the plastid. This review will survey our current understanding of mitochondrial and plastid functions with a view to identify processes that are or have a potential to be targets for antimalarial drugs.
Vaidya
Akhil B
AB
Division of Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, USA. av27@drexel.edu
D000818:Animals; D000962:Antimalarials / Q000378:metabolism / Q000627:therapeutic use*; D002467:Cell Nucleus / Q000235:genetics; D002875:Chromosomes / Q000235:genetics; D004579:Electron Transport; D005227:Fatty Acids / Q000096:biosynthesis; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D008954:Models, Biological; D018087:Plastids / Q000187:drug effects / Q000378:metabolism*; D013559:Symbiosis; D013729:Terpenes / Q000378:metabolism
D000962:Antimalarials; D005227:Fatty Acids; D013729:Terpenes