{"doi":"10.1128/mbio.01718-23","title":"A patatin-like phospholipase is important for mitochondrial function in malaria parasites","abstract":"ABSTRACT Plasmodium parasites rely on a functional electron transport chain (ETC) within their mitochondrion for proliferation, and compounds targeting mitochondrial functions are validated antimalarials. Here, we localize Plasmodium falciparum patatin-like phospholipase 2 ( Pf PNPLA2, PF3D7_1358000) to the mitochondrion and reveal that disruption of the Pf PNPLA2 gene impairs asexual replication. Pf PNPLA2-null parasites are hypersensitive to proguanil and inhibitors of the mitochondrial ETC, including atovaquone. In addition, Pf PNPLA2-deficient parasites show reduced mitochondrial respiration and reduced mitochondrial membrane potential, indicating that disruption of Pf PNPLA2 leads to a defect in the parasite ETC. Lipidomic analysis of the mitochondrial phospholipid cardiolipin (CL) reveals that loss of Pf PNPLA2 is associated with a moderate shift toward shorter-chained and more saturated CL species, implying a contribution of Pf PNPLA2 to CL remodeling. Pf PNPLA2-deficient parasites display profound defects in gametocytogenesis, underlining the importance of a functional mitochondrial ETC during both the asexual and sexual development of the parasite. IMPORTANCE For their proliferation within red blood cells, malaria parasites depend on a functional electron transport chain (ETC) within their mitochondrion, which is the target of several antimalarial drugs. Here, we have used gene disruption to identify a patatin-like phospholipase, Pf PNPLA2, as important for parasite replication and mitochondrial function in Plasmodium falciparum . Parasites lacking Pf PNPLA2 show defects in their ETC and become hypersensitive to mitochondrion-targeting drugs. Furthermore, Pf PNPLA2-deficient parasites show differences in the composition of their cardiolipins, a unique class of phospholipids with key roles in mitochondrial functions. Finally, we demonstrate that parasites devoid of Pf PNPLA2 have a defect in gametocyte maturation, underlining the importance of a functional ETC for parasite transmission to the mosquito vector.","journal":"mBio","year":2023,"id":348620,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.956,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":811329,"name":"Abhinay Ramaprasad","orcid":"0000-0001-9372-5526","position":1,"is_corresponding":false},{"id":811912,"name":"Sabrina Bielfeld","orcid":null,"position":2,"is_corresponding":false},{"id":1091253,"name":"Yvonne Wohlfarter","orcid":"0000-0002-0988-9411","position":3,"is_corresponding":false},{"id":457026,"name":"Bohumil Maco","orcid":"0000-0001-8444-313X","position":4,"is_corresponding":false},{"id":1091851,"name":"Korbinian Niedermüller","orcid":null,"position":5,"is_corresponding":false},{"id":811330,"name":"Louisa Wilcke","orcid":"0000-0002-3572-272X","position":6,"is_corresponding":false},{"id":1091254,"name":"Joachim Kloehn","orcid":"0000-0002-6366-8599","position":7,"is_corresponding":false},{"id":232563,"name":"Markus A. Keller","orcid":"0000-0002-8654-9920","position":8,"is_corresponding":false},{"id":457029,"name":"Dominique Soldati‐Favre","orcid":"0000-0003-4156-2109","position":9,"is_corresponding":false},{"id":699702,"name":"Michael J. Blackman","orcid":"0000-0002-7442-3810","position":10,"is_corresponding":false},{"id":457027,"name":"Tim‐Wolf Gilberger","orcid":"0000-0002-7965-8272","position":11,"is_corresponding":false},{"id":725554,"name":"Paul-Christian Burda","orcid":"0000-0003-0461-4352","position":12,"is_corresponding":false},{"id":725552,"name":"Emma Pietsch","orcid":"0000-0003-4744-1666","position":0,"is_corresponding":true}],"reference_count":80,"raw_metadata":null,"created_at":"2026-07-19T01:12:10.335697Z","pmid":"37882543","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}