Putative metabolic roles of the mitochondria in asexual blood stages and gametocytes of Plasmodium falciparum
Krungkrai J1,Kanchanaphum P1,Pongsabut S1,Krungkrai SR2 1 Department of Biochemistry,Faculty of Medicine,Chulalongkorn University,Rama 4 Road,Bangkok 10330, Thailand 2 Unit of Biochemistry,Department of Medical Science,Faculty of Science,Rangsit University,Paholyothin Road, Patumthani 12000,Thailand
Upon infection into human red cell,Plasmodium falciparum differentiates into asexual and sexual(gametocyte) stages.The mitochondrion is a tubular-cristate organelle,functionally and structurally different between the two stages.Genes and proteins involving metabolic and functional roles,protein targeting and import to this organelle, are comprehensively reviewed.The genes and proteins of the electron transport system are identified, partially characterized in human and rodent malaria parasites consisting of a single subunit of NADH dehydrogenase, two subunits of succinate dehydrogenase,cytochrome C reductase and cytochrome Coxidase.One of the primary functional roles of the mitochondrion in the parasite is the coordination of pyrimidine biosynthesis, the electron transport system and oxygen utilization through dihydroorotate dehydrogenase.All enzymes of tricarboxylic acid cycle,pyruvate dehydrogenase complex and some enzymes of ATP synthase,are identified and partially characterized using the completed P.falciparum genome.Some metabolic and functional roles of the organelle include oxidative phosphorylation,ubiquinone and heme biosynthesis,antioxidant defense and redox balance.Recent physiological studies involve membrane potential maintenance,cellular signaling and cation homeostasis.The organelle is a target for antimalarial drug,i.e.atovaquone.Based on the lines of evidence, we hypothesize that the parasite exhibits metabolic adaptation of the underdeveloped mitochondrial organelle to life in the mosquito vector and the human host.
【Fund】： the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases(CHEMAL);; the National Science and Technology Development Agency of Thailand (Career Development Award);; the Thailand Research Fund(Basic Research)
【CateGory Index】： R382
【CateGory Index】： R382