Autophagy protein Atg7 is essential for maintaining malaria parasite cellular homeostasis and organelle biogenesis
ABSTRACT Plasmodium parasites have a complex life cycle that transitions between mosquito and mammalian hosts, and undergo continuous cellular remodeling to adapt to various drastic environments. Following hepatocyte invasion, the parasite discards superfluous organelles for intracellular replicatio...
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American Society for Microbiology
2025-02-01
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| Series: | mBio |
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| Online Access: | https://journals.asm.org/doi/10.1128/mbio.02735-24 |
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| author | Akancha Mishra Suryansh Rajput Pratik Narain Srivastava H. Shabeer Ali Satish Mishra |
| author_facet | Akancha Mishra Suryansh Rajput Pratik Narain Srivastava H. Shabeer Ali Satish Mishra |
| author_sort | Akancha Mishra |
| collection | DOAJ |
| description | ABSTRACT Plasmodium parasites have a complex life cycle that transitions between mosquito and mammalian hosts, and undergo continuous cellular remodeling to adapt to various drastic environments. Following hepatocyte invasion, the parasite discards superfluous organelles for intracellular replication, and the remnant organelles undergo extensive branching and mature into hepatic merozoites. Autophagy is a ubiquitous eukaryotic process that permits the recycling of intracellular components. Here, we show that the Plasmodium berghei autophagy-related E1-like enzyme Atg7 is expressed in the blood, sporozoites, and liver stages, localized to the parasite cytosol, and is essential for the localization of Atg8 on the membrane and the development of parasite blood and liver forms. We found that depleting Atg7 abolishes Atg8 lipidation, exocytosis of micronemes, organelle biogenesis, and the formation of merozoites during liver-stage development. Overall, this study establishes the essential functions of Atg7 in Plasmodium blood and liver stages, and highlights its role in maintaining the parasite’s cellular homeostasis and organelle biogenesis.IMPORTANCEThe malaria life cycle involves two hosts, mosquitoes and vertebrates. Plasmodium parasites undergo complex intracellular and extracellular stages during this transition. Here, we report that an autophagy-related E1-like enzyme Atg7 is required to conjugate Atg8 on the apicoplast membrane. Atg7 depletion in Plasmodium berghei resulted in the loss of Atg8 lipidation and multiple defects like clearance of micronemes, organelle biogenesis, and maturation of hepatic schizonts during liver-stage development. The essentiality of Plasmodium Atg7 in blood and liver stages suggests it is a prospective target for developing autophagy-specific inhibitors. These results highlight the importance of autophagy in malaria parasite development. |
| format | Article |
| id | doaj-art-0156992cf318451a9afcd902b8b69d02 |
| institution | Kabale University |
| issn | 2150-7511 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj-art-0156992cf318451a9afcd902b8b69d022025-02-05T14:00:48ZengAmerican Society for MicrobiologymBio2150-75112025-02-0116210.1128/mbio.02735-24Autophagy protein Atg7 is essential for maintaining malaria parasite cellular homeostasis and organelle biogenesisAkancha Mishra0Suryansh Rajput1Pratik Narain Srivastava2H. Shabeer Ali3Satish Mishra4Division of Molecular Microbiology and Immunology, CSIR-Central Drug Research Institute, Lucknow, IndiaDivision of Molecular Microbiology and Immunology, CSIR-Central Drug Research Institute, Lucknow, IndiaDivision of Molecular Microbiology and Immunology, CSIR-Central Drug Research Institute, Lucknow, IndiaDivision of Molecular Microbiology and Immunology, CSIR-Central Drug Research Institute, Lucknow, IndiaDivision of Molecular Microbiology and Immunology, CSIR-Central Drug Research Institute, Lucknow, IndiaABSTRACT Plasmodium parasites have a complex life cycle that transitions between mosquito and mammalian hosts, and undergo continuous cellular remodeling to adapt to various drastic environments. Following hepatocyte invasion, the parasite discards superfluous organelles for intracellular replication, and the remnant organelles undergo extensive branching and mature into hepatic merozoites. Autophagy is a ubiquitous eukaryotic process that permits the recycling of intracellular components. Here, we show that the Plasmodium berghei autophagy-related E1-like enzyme Atg7 is expressed in the blood, sporozoites, and liver stages, localized to the parasite cytosol, and is essential for the localization of Atg8 on the membrane and the development of parasite blood and liver forms. We found that depleting Atg7 abolishes Atg8 lipidation, exocytosis of micronemes, organelle biogenesis, and the formation of merozoites during liver-stage development. Overall, this study establishes the essential functions of Atg7 in Plasmodium blood and liver stages, and highlights its role in maintaining the parasite’s cellular homeostasis and organelle biogenesis.IMPORTANCEThe malaria life cycle involves two hosts, mosquitoes and vertebrates. Plasmodium parasites undergo complex intracellular and extracellular stages during this transition. Here, we report that an autophagy-related E1-like enzyme Atg7 is required to conjugate Atg8 on the apicoplast membrane. Atg7 depletion in Plasmodium berghei resulted in the loss of Atg8 lipidation and multiple defects like clearance of micronemes, organelle biogenesis, and maturation of hepatic schizonts during liver-stage development. The essentiality of Plasmodium Atg7 in blood and liver stages suggests it is a prospective target for developing autophagy-specific inhibitors. These results highlight the importance of autophagy in malaria parasite development.https://journals.asm.org/doi/10.1128/mbio.02735-24Atg7Atg8apicoplastERautophagyPlasmodium |
| spellingShingle | Akancha Mishra Suryansh Rajput Pratik Narain Srivastava H. Shabeer Ali Satish Mishra Autophagy protein Atg7 is essential for maintaining malaria parasite cellular homeostasis and organelle biogenesis mBio Atg7 Atg8 apicoplast ER autophagy Plasmodium |
| title | Autophagy protein Atg7 is essential for maintaining malaria parasite cellular homeostasis and organelle biogenesis |
| title_full | Autophagy protein Atg7 is essential for maintaining malaria parasite cellular homeostasis and organelle biogenesis |
| title_fullStr | Autophagy protein Atg7 is essential for maintaining malaria parasite cellular homeostasis and organelle biogenesis |
| title_full_unstemmed | Autophagy protein Atg7 is essential for maintaining malaria parasite cellular homeostasis and organelle biogenesis |
| title_short | Autophagy protein Atg7 is essential for maintaining malaria parasite cellular homeostasis and organelle biogenesis |
| title_sort | autophagy protein atg7 is essential for maintaining malaria parasite cellular homeostasis and organelle biogenesis |
| topic | Atg7 Atg8 apicoplast ER autophagy Plasmodium |
| url | https://journals.asm.org/doi/10.1128/mbio.02735-24 |
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