Pivotal roles of Plasmodium falciparum lysophospholipid acyltransferase 1 in cell cycle progression and cytostome internalization
Abstract The rapid intraerythrocytic replication of Plasmodium falciparum, a deadly species of malaria parasite, requires a quick but constant supply of phospholipids to support marked cell membrane expansion. In the malarial parasite, many enzymes functioning in phospholipid synthesis pathway have...
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Nature Portfolio
2025-01-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07564-4 |
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| author | Junpei Fukumoto Minako Yoshida Suzumi M. Tokuoka Eri Saki H. Hayakawa Shinya Miyazaki Takaya Sakura Daniel Ken Inaoka Kiyoshi Kita Jiro Usukura Hideo Shindou Fuyuki Tokumasu |
| author_facet | Junpei Fukumoto Minako Yoshida Suzumi M. Tokuoka Eri Saki H. Hayakawa Shinya Miyazaki Takaya Sakura Daniel Ken Inaoka Kiyoshi Kita Jiro Usukura Hideo Shindou Fuyuki Tokumasu |
| author_sort | Junpei Fukumoto |
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| description | Abstract The rapid intraerythrocytic replication of Plasmodium falciparum, a deadly species of malaria parasite, requires a quick but constant supply of phospholipids to support marked cell membrane expansion. In the malarial parasite, many enzymes functioning in phospholipid synthesis pathway have not been identified or characterized. Here, we identify P. falciparum lysophospholipid acyltransferase 1 (PfLPLAT1) and show that PfLPLAT1 is vital for asexual parasite cell cycle progression and cytostome internalization. Deficiency in PfLPLAT1 results in decreased parasitemia and prevents transition to the schizont stage. Parasites lacking PfLPLAT1 also exhibit distinctive omega-shaped vacuoles, indicating disrupted cytostome function. Transcriptomic analyses suggest that this deficiency impacts DNA replication and cell cycle regulation. Mass spectrometry-based enzyme assay and lipidomic analysis demonstrate that recombinant PfLPLAT1 exhibits lysophospholipid acyltransferase activity with a preference for unsaturated fatty acids as its acyl donors and lysophosphatidic acids as an acceptor, with its conditional knockout leading to abnormal lipid composition and marked morphological and developmental changes including stage arrest. These findings highlight PfLPLAT1 as a potential target for antimalarial therapy, particularly due to its unique role and divergence from human orthologs. |
| format | Article |
| id | doaj-art-7d22d59883ee4ee897e27e6ef2ddd8ab |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-7d22d59883ee4ee897e27e6ef2ddd8ab2025-02-02T12:37:23ZengNature PortfolioCommunications Biology2399-36422025-01-018111710.1038/s42003-025-07564-4Pivotal roles of Plasmodium falciparum lysophospholipid acyltransferase 1 in cell cycle progression and cytostome internalizationJunpei Fukumoto0Minako Yoshida1Suzumi M. Tokuoka2Eri Saki H. Hayakawa3Shinya Miyazaki4Takaya Sakura5Daniel Ken Inaoka6Kiyoshi Kita7Jiro Usukura8Hideo Shindou9Fuyuki Tokumasu10Department of Cellular Architecture Studies, Division of Shionogi Global Infectious Diseases Division, Institute of Tropical Medicine (NEKKEN), Nagasaki UniversityDepartment of Cellular Architecture Studies, Division of Shionogi Global Infectious Diseases Division, Institute of Tropical Medicine (NEKKEN), Nagasaki UniversityDepartment of Lipidomics, Graduate School of Medicine, University of TokyoDivision of Medical Zoology, Department of Infection and Immunity, Jichi Medical UniversityDepartment of Cellular Architecture Studies, Division of Shionogi Global Infectious Diseases Division, Institute of Tropical Medicine (NEKKEN), Nagasaki UniversityDepartment of Molecular Infection Dynamics, Division of Shionogi Global Infectious Diseases Division, Institute of Tropical Medicine (NEKKEN), Nagasaki UniversityDepartment of Molecular Infection Dynamics, Division of Shionogi Global Infectious Diseases Division, Institute of Tropical Medicine (NEKKEN), Nagasaki UniversitySchool of Tropical Medicine and Global Health, Nagasaki UniversityInstitute of Materials and Systems for Sustainability, Nagoya UniversityDepartment of Lipid Life Science, National Center for Global Health and MedicineDepartment of Cellular Architecture Studies, Division of Shionogi Global Infectious Diseases Division, Institute of Tropical Medicine (NEKKEN), Nagasaki UniversityAbstract The rapid intraerythrocytic replication of Plasmodium falciparum, a deadly species of malaria parasite, requires a quick but constant supply of phospholipids to support marked cell membrane expansion. In the malarial parasite, many enzymes functioning in phospholipid synthesis pathway have not been identified or characterized. Here, we identify P. falciparum lysophospholipid acyltransferase 1 (PfLPLAT1) and show that PfLPLAT1 is vital for asexual parasite cell cycle progression and cytostome internalization. Deficiency in PfLPLAT1 results in decreased parasitemia and prevents transition to the schizont stage. Parasites lacking PfLPLAT1 also exhibit distinctive omega-shaped vacuoles, indicating disrupted cytostome function. Transcriptomic analyses suggest that this deficiency impacts DNA replication and cell cycle regulation. Mass spectrometry-based enzyme assay and lipidomic analysis demonstrate that recombinant PfLPLAT1 exhibits lysophospholipid acyltransferase activity with a preference for unsaturated fatty acids as its acyl donors and lysophosphatidic acids as an acceptor, with its conditional knockout leading to abnormal lipid composition and marked morphological and developmental changes including stage arrest. These findings highlight PfLPLAT1 as a potential target for antimalarial therapy, particularly due to its unique role and divergence from human orthologs.https://doi.org/10.1038/s42003-025-07564-4 |
| spellingShingle | Junpei Fukumoto Minako Yoshida Suzumi M. Tokuoka Eri Saki H. Hayakawa Shinya Miyazaki Takaya Sakura Daniel Ken Inaoka Kiyoshi Kita Jiro Usukura Hideo Shindou Fuyuki Tokumasu Pivotal roles of Plasmodium falciparum lysophospholipid acyltransferase 1 in cell cycle progression and cytostome internalization Communications Biology |
| title | Pivotal roles of Plasmodium falciparum lysophospholipid acyltransferase 1 in cell cycle progression and cytostome internalization |
| title_full | Pivotal roles of Plasmodium falciparum lysophospholipid acyltransferase 1 in cell cycle progression and cytostome internalization |
| title_fullStr | Pivotal roles of Plasmodium falciparum lysophospholipid acyltransferase 1 in cell cycle progression and cytostome internalization |
| title_full_unstemmed | Pivotal roles of Plasmodium falciparum lysophospholipid acyltransferase 1 in cell cycle progression and cytostome internalization |
| title_short | Pivotal roles of Plasmodium falciparum lysophospholipid acyltransferase 1 in cell cycle progression and cytostome internalization |
| title_sort | pivotal roles of plasmodium falciparum lysophospholipid acyltransferase 1 in cell cycle progression and cytostome internalization |
| url | https://doi.org/10.1038/s42003-025-07564-4 |
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