HDP - A novel heme detoxification protein from the malaria parasite

Dewal Jani, Rana Nagarkatti, Wandy Beatty, Ross Angel, Carla Slebodnick, John Andersen, Sanjai Kumar, Dharmendar Rathore

Research output: Contribution to journalArticlepeer-review

121 Scopus citations

Abstract

When malaria parasites infect host red blood cells (RBC) and proteolyze hemoglobin, a unique, albeit poorly understood parasite-specific mechanism, detoxifies released heme into hemozoin (Hz). Here, we report the identification and characterization of a novel Plasmodium Heme Detoxification Protein (HDP) that is extremely potent in converting heme into Hz. HDP is functionally conserved across Plasmodium genus and its gene locus could not be disrupted. Once expressed, the parasite utilizes a circuitous "Outbound-Inbound" trafficking route by initially secreting HDP into the cytosol of infected RBC. A subsequent endocytosis of host cytosol (and hemoglobin) delivers HDP to the food vacuole (FV), the site of Hz formation. As Hz formation is critical for survival, involvement of HDP in this process suggests that it could be a malaria drug target.

Original languageEnglish
Article numbere1000053
JournalPLoS pathogens
Volume4
Issue number4
DOIs
StatePublished - Apr 2008

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