Open AccessHeme Detoxification Protein ( Pf HDP ) is essential for the hemoglobin uptake and metabolism in Plasmodium falciparum
Author(s) -
Gupta Priya,
Pandey Rajan,
Thakur Vandana,
Parveen Sadaf,
Kaur Inderjeet,
Panda Ashutosh,
Bishi Rashmita,
Mehrotra Sonali,
Akhtar Asif,
Gupta Dinesh,
Mohmmed Asif,
Malhotra Pawan
Publication year - 2022
Publication title -
faseb bioadvances
Language(s) - English
Resource type - Journals
ISSN - 2573-9832
DOI - 10.1096/fba.2022-00021
Subject(s) - plasmodium falciparum , heme , hemoglobin , detoxification (alternative medicine) , metabolism , biochemistry , chemistry , microbiology and biotechnology , biology , malaria , enzyme , medicine , immunology , alternative medicine , pathology
Hemoglobin degradation is crucial for the growth and survival of Plasmodium falciparum in human erythrocytes. Although the process of Hb degradation has been studied in detail, the mechanisms of Hb uptake remain ambiguous to date. Here, we characterized Heme Detoxification Protein ( Pf HDP); a protein localized in the parasitophorus vacuole, parasite food vacuole, and infected erythrocyte cytosol for its role in Hb uptake. Immunoprecipitation of Pf HDP‐GFP fusion protein from a transgenic line using GFP trap beads showed the association of Pf HDP with Hb as well as with the members of PTEX translocon complex. Association of Pf HDP with Hb or Pf exp‐2, a component of translocon complex was confirmed by protein–protein interaction and immunolocalization tools. Based on these associations, we studied the role of Pf HDP in Hb uptake using the Pf HDP‐HA‐GlmS transgenic parasites line. Pf HDP knockdown significantly reduced the Hb uptake in these transgenic parasites in comparison to the wild‐type parasites. Morphological analysis of Pf HDP‐HA‐GlmS transgenic parasites in the presence of GlcN showed food vacuole abnormalities and parasite stress, thereby causing a growth defect in the development of these parasites. Transient knockdown of a member of translocon complex, Pf HSP101 in HSP101‐DDDHA parasites also showed a decreased uptake of Hb inside the parasite. Together, these results advocate an interaction between Pf HDP and the translocon complex at the parasitophorus vacuole membrane and also suggest a role for Pf HDP in the uptake of Hb and parasite development. The study thus reveals new insights into the function of Pf HDP, making it an extremely important target for developing new antimalarials.