{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T17:06:51Z","timestamp":1770743211965,"version":"3.49.0"},"reference-count":25,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T00:00:00Z","timestamp":1696982400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100010803","name":"Department of Biotechnology, Government of West Bengal","doi-asserted-by":"publisher","award":["Centre of Excellence grant (BT\/COE\/34\/SP15138\/2015)"],"award-info":[{"award-number":["Centre of Excellence grant (BT\/COE\/34\/SP15138\/2015)"]}],"id":[{"id":"10.13039\/501100010803","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010803","name":"Department of Biotechnology, Government of West Bengal","doi-asserted-by":"publisher","award":["Flagship Grant (#BT\/IC\u201006\/003\/91)"],"award-info":[{"award-number":["Flagship Grant (#BT\/IC\u201006\/003\/91)"]}],"id":[{"id":"10.13039\/501100010803","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001843","name":"Science and Engineering Research Board","doi-asserted-by":"publisher","award":["CRG\/2022\/002655"],"award-info":[{"award-number":["CRG\/2022\/002655"]}],"id":[{"id":"10.13039\/501100001843","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Metabolic pathways and proteins responsible for maintaining mitochondrial dynamics and homeostasis in the\n                    <jats:italic>Plasmodium<\/jats:italic>\n                    parasite, the causative agent of malaria, remain to be elucidated. Here, we identified and functionally characterized a novel OPA3\u2010like domain\u2010containing protein in\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    (\n                    <jats:italic>Pf<\/jats:italic>\n                    OPA3). We show that\n                    <jats:italic>Pf<\/jats:italic>\n                    OPA3 is expressed in the intraerythrocytic stages of the parasite and localizes to the mitochondria. Inducible knock\u2010down of\n                    <jats:italic>Pf<\/jats:italic>\n                    OPA3 using GlmS ribozyme hindered the normal intraerythrocytic cycle of the parasites; specifically,\n                    <jats:italic>Pf<\/jats:italic>\n                    OPA3\u2010iKD disrupted parasite development as well as parasite division and segregation at schizont stages, which resulted in a drastic reduction in the number of merozoites progenies. Parasites lacking\n                    <jats:italic>Pf<\/jats:italic>\n                    OPA3 show severe defects in the development of functional mitochondria; the mitochondria showed reduced activity of mtETC but not ATP synthesis, as evidenced by reduced activity of complex III of the mtETC, and increased sensitivity for drugs targeting DHODH as well as complex III, but not to the drugs targeting complex V. Further,\n                    <jats:italic>Pf<\/jats:italic>\n                    OPA3 downregulation leads to reduction in the level of mitochondrial proton transport uncoupling protein (\n                    <jats:italic>Pf<\/jats:italic>\n                    UCP) to compensate reduced activity of complex III and maintain proton efflux across the inner membrane. The reduced activity of DHODH, which is responsible for pyrimidine biosynthesis required for nuclear DNA synthesis, resulted in a significant reduction in parasite nuclear division and generation of progeny. In conclusion, we show that\n                    <jats:italic>Pf<\/jats:italic>\n                    OPA3 is essential for the functioning of mtETC and homeostasis required for the development of functional mitochondria as well as for parasite segregation, and thus\n                    <jats:italic>Pf<\/jats:italic>\n                    OPA3 is crucial for parasite survival during blood stages.\n                  <\/jats:p>","DOI":"10.1096\/fj.202201386rr","type":"journal-article","created":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T11:06:44Z","timestamp":1697022404000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<i>Plasmodium falciparum<\/i>\n                    <scp>OPA3<\/scp>\n                    \u2010like protein (\n                    <scp>\n                      <i>Pf<\/i>\n                      OPA3\n                    <\/scp>\n                    ) is essential for maintenance of mitochondrial homeostasis and parasite proliferation"],"prefix":"10.1096","volume":"37","author":[{"given":"Monika","family":"Narwal","sequence":"first","affiliation":[{"name":"Parasite Cell Biology Group International Centre for Genetic Engineering and Biotechnology  New Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shilpi","family":"Jain","sequence":"additional","affiliation":[{"name":"Parasite Cell Biology Group International Centre for Genetic Engineering and Biotechnology  New Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sumit","family":"Rathore","sequence":"additional","affiliation":[{"name":"Department of Biotechnology All India Institute of Medical Sciences  New\u00a0Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0239-1979","authenticated-orcid":false,"given":"Asif","family":"Mohmmed","sequence":"additional","affiliation":[{"name":"Parasite Cell Biology Group International Centre for Genetic Engineering and Biotechnology  New Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,10,11]]},"reference":[{"key":"e_1_2_10_2_1","volume-title":"World Malaria Report 2021","author":"WHO","year":"2021"},{"key":"e_1_2_10_3_1","volume-title":"World Malaria Report 2020: 20\u2009Years of Global Progress and 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