title: Is the Mitochondrion a Good Malaria Drug Target?
abstract: Rapid emergence of resistance to atovaquone, which targets electron transport in the malaria parasite mitochondrion, relegated its use to prophylaxis and even cast a shadow over the development of drugs targeting other parasite mitochondrial pathways. Here we argue for a renewed focus on the mitochondrion as a drug target, focusing particularly on the issues of resistance. We posit a hypothesis for why atovaquone resistance emerges so quickly, and we explain how facile acquisition of resistance is apparently offset by an inability of parasites to spread this resistance. We also explore the utility and resistance issues for emerging new drugs targeting parasite mitochondria, concluding that the mitochondrion is indeed an excellent target.
authors: School of BioSciences, University of Melbourne, VIC 3010, Australia.
authors: Christopher D
authors: CD
authors: Goodman
authors: School of BioSciences, University of Melbourne, VIC 3010, Australia.
authors: Hayley D
authors: HD
authors: Buchanan
authors: School of BioSciences, University of Melbourne, VIC 3010, Australia. Electronic address: gim@unimelb.edu.au.
authors: Geoffrey I
authors: GI
authors: McFadden
mesh_terms: D000962:Antimalarials / Q000494:pharmacology; D053626:Atovaquone / Q000494:pharmacology; D016503:Drug Delivery Systems; D004351:Drug Resistance; D006801:Humans; D008288:Malaria / Q000188:drug therapy / Q000517:prevention & control*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000187:drug effects
chemical_list: D000962:Antimalarials; D053626:Atovaquone