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

  • Nagaraj V
  • Arumugam R
  • Prasad D
 et al. 
  • 32

    Readers

    Mendeley users who have this article in their library.
  • 21

    Citations

    Citations of this article.

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. © 2010 Elsevier B.V.

Author-supplied keywords

  • Anaerobic
  • Electron transport chain
  • Heme
  • Plasmodium falciparum
  • Protoporphyrinogen oxidase

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • Viswanathan Arun Nagaraj

  • Rajavel Arumugam

  • Dasari Prasad

  • Pundi N. Rangarajan

  • Govindarajan Padmanaban

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free