Heme Detoxification Protein (PfHDP) is essential for the hemoglobin uptake and metabolism in Plasmodium falciparum
Abstract 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 (PfHDP);...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-10-01
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| Series: | FASEB BioAdvances |
| Online Access: | https://doi.org/10.1096/fba.2022-00021 |
| _version_ | 1817968738779004928 |
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| author | Priya Gupta Rajan Pandey Vandana Thakur Sadaf Parveen Inderjeet Kaur Ashutosh Panda Rashmita Bishi Sonali Mehrotra Asif Akhtar Dinesh Gupta Asif Mohmmed Pawan Malhotra |
| author_facet | Priya Gupta Rajan Pandey Vandana Thakur Sadaf Parveen Inderjeet Kaur Ashutosh Panda Rashmita Bishi Sonali Mehrotra Asif Akhtar Dinesh Gupta Asif Mohmmed Pawan Malhotra |
| author_sort | Priya Gupta |
| collection | DOAJ |
| description | Abstract 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 (PfHDP); a protein localized in the parasitophorus vacuole, parasite food vacuole, and infected erythrocyte cytosol for its role in Hb uptake. Immunoprecipitation of PfHDP‐GFP fusion protein from a transgenic line using GFP trap beads showed the association of PfHDP with Hb as well as with the members of PTEX translocon complex. Association of PfHDP with Hb or Pfexp‐2, a component of translocon complex was confirmed by protein–protein interaction and immunolocalization tools. Based on these associations, we studied the role of PfHDP in Hb uptake using the PfHDP‐HA‐GlmS transgenic parasites line. PfHDP knockdown significantly reduced the Hb uptake in these transgenic parasites in comparison to the wild‐type parasites. Morphological analysis of PfHDP‐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, PfHSP101 in HSP101‐DDDHA parasites also showed a decreased uptake of Hb inside the parasite. Together, these results advocate an interaction between PfHDP and the translocon complex at the parasitophorus vacuole membrane and also suggest a role for PfHDP in the uptake of Hb and parasite development. The study thus reveals new insights into the function of PfHDP, making it an extremely important target for developing new antimalarials. |
| first_indexed | 2024-04-13T20:12:47Z |
| format | Article |
| id | doaj.art-5b0ffeec1a6849c0b030b340e989d3bf |
| institution | Directory Open Access Journal |
| issn | 2573-9832 |
| language | English |
| last_indexed | 2024-04-13T20:12:47Z |
| publishDate | 2022-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | FASEB BioAdvances |
| spelling | doaj.art-5b0ffeec1a6849c0b030b340e989d3bf2022-12-22T02:31:48ZengWileyFASEB BioAdvances2573-98322022-10-0141066267410.1096/fba.2022-00021Heme Detoxification Protein (PfHDP) is essential for the hemoglobin uptake and metabolism in Plasmodium falciparumPriya Gupta0Rajan Pandey1Vandana Thakur2Sadaf Parveen3Inderjeet Kaur4Ashutosh Panda5Rashmita Bishi6Sonali Mehrotra7Asif Akhtar8Dinesh Gupta9Asif Mohmmed10Pawan Malhotra11Malaria Biology Group, International Centre for Genetic Engineering and Biotechnology New Delhi IndiaTranslational Bioinformatics Group International Centre for Genetic Engineering and Biotechnology New Delhi IndiaParasite Cell Biology Group International Centre for Genetic Engineering and Biotechnology New Delhi IndiaMalaria Biology Group, International Centre for Genetic Engineering and Biotechnology New Delhi IndiaMalaria Biology Group, International Centre for Genetic Engineering and Biotechnology New Delhi IndiaMalaria Biology Group, International Centre for Genetic Engineering and Biotechnology New Delhi IndiaMalaria Biology Group, International Centre for Genetic Engineering and Biotechnology New Delhi IndiaMalaria Biology Group, International Centre for Genetic Engineering and Biotechnology New Delhi IndiaMalaria Biology Group, International Centre for Genetic Engineering and Biotechnology New Delhi IndiaTranslational Bioinformatics Group International Centre for Genetic Engineering and Biotechnology New Delhi IndiaParasite Cell Biology Group International Centre for Genetic Engineering and Biotechnology New Delhi IndiaMalaria Biology Group, International Centre for Genetic Engineering and Biotechnology New Delhi IndiaAbstract 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 (PfHDP); a protein localized in the parasitophorus vacuole, parasite food vacuole, and infected erythrocyte cytosol for its role in Hb uptake. Immunoprecipitation of PfHDP‐GFP fusion protein from a transgenic line using GFP trap beads showed the association of PfHDP with Hb as well as with the members of PTEX translocon complex. Association of PfHDP with Hb or Pfexp‐2, a component of translocon complex was confirmed by protein–protein interaction and immunolocalization tools. Based on these associations, we studied the role of PfHDP in Hb uptake using the PfHDP‐HA‐GlmS transgenic parasites line. PfHDP knockdown significantly reduced the Hb uptake in these transgenic parasites in comparison to the wild‐type parasites. Morphological analysis of PfHDP‐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, PfHSP101 in HSP101‐DDDHA parasites also showed a decreased uptake of Hb inside the parasite. Together, these results advocate an interaction between PfHDP and the translocon complex at the parasitophorus vacuole membrane and also suggest a role for PfHDP in the uptake of Hb and parasite development. The study thus reveals new insights into the function of PfHDP, making it an extremely important target for developing new antimalarials.https://doi.org/10.1096/fba.2022-00021 |
| spellingShingle | Priya Gupta Rajan Pandey Vandana Thakur Sadaf Parveen Inderjeet Kaur Ashutosh Panda Rashmita Bishi Sonali Mehrotra Asif Akhtar Dinesh Gupta Asif Mohmmed Pawan Malhotra Heme Detoxification Protein (PfHDP) is essential for the hemoglobin uptake and metabolism in Plasmodium falciparum FASEB BioAdvances |
| title | Heme Detoxification Protein (PfHDP) is essential for the hemoglobin uptake and metabolism in Plasmodium falciparum |
| title_full | Heme Detoxification Protein (PfHDP) is essential for the hemoglobin uptake and metabolism in Plasmodium falciparum |
| title_fullStr | Heme Detoxification Protein (PfHDP) is essential for the hemoglobin uptake and metabolism in Plasmodium falciparum |
| title_full_unstemmed | Heme Detoxification Protein (PfHDP) is essential for the hemoglobin uptake and metabolism in Plasmodium falciparum |
| title_short | Heme Detoxification Protein (PfHDP) is essential for the hemoglobin uptake and metabolism in Plasmodium falciparum |
| title_sort | heme detoxification protein pfhdp is essential for the hemoglobin uptake and metabolism in plasmodium falciparum |
| url | https://doi.org/10.1096/fba.2022-00021 |
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