Protoporphyrinogen IX oxidase from Plasmodium falciparum is anaerobic and is localized to the mitochondrion

Nagaraj, Viswanathan Arun and Arumugam, Rajavel and Prasad, Dasari and Rangarajan, Pundi N and Padmanaban, Govindarajan (2010) Protoporphyrinogen IX oxidase from Plasmodium falciparum is anaerobic and is localized to the mitochondrion. In: Molecular and Biochemical Parasitology, 174 (1). pp. 44-52.

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Abstract

Earlier studies in this laboratory had shown that the malarial parasite can synthesize heme de novo and inhibition of the pathway leads to death of the parasite. It has been proposed that the pathway for the biosynthesis of heme in Plasmodium falciparum is unique involving three different cellular compartments, namely mitochondrion, apicoplast and cytosol. Experimental evidences are now available for the functionality and localization of all the enzymes of this pathway, except protoporphyrinogen IX oxidase (PfPPO), the penultimate enzyme. In the present study. PfPPO has been cloned, expressed and shown to be localized to the mitochondrion by immunofluorescence microscopy. Interestingly, the enzyme has been found to be active only under anaerobic conditions and is dependent on electron transport chain (ETC) acceptors for its activity. The native enzyme present in the parasite is inhibited by the ETC inhibitors, atovaquone and antimycin. Atovaquone, a well known inhibitor of parasite dihydroorotate dehydrogenase, dependent on the ETC, inhibits synthesis of heme as well in P. falciparum culture. A model is proposed to explain the ETC dependence of both the pyrimidine and heme-biosynthetic pathways in P. falciparum. (C) 2010 Elsevier B.V. All rights reserved.

Item Type:	Journal Article
Publication:	Molecular and Biochemical Parasitology
Publisher:	Elsevier Science
Additional Information:	Copyright of this article belongs to Elsevier Science.
Keywords:	Heme;Plasmodium falciparum; Protoporphyrinogen oxidase; Anaerobic; Electron transport chain.
Department/Centre:	Division of Biological Sciences > Biochemistry
Date Deposited:	18 Oct 2010 07:41
Last Modified:	18 Oct 2010 07:41
URI:	http://eprints.iisc.ac.in/id/eprint/33125

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