{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T22:22:22Z","timestamp":1788474142964,"version":"build-2803163510"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T00:00:00Z","timestamp":1725408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Parasitol."],"abstract":"<jats:p>Artemisinin-based treatments (ACTs) are the first therapy currently used to treat malaria produced by <jats:italic>Plasmodium falciparum<\/jats:italic>. However, in recent years, increasing evidence shows that some strains of <jats:italic>P. falciparum<\/jats:italic> are less susceptible to ACT in the Southeast Asian region. A data reanalysis of several omics approaches currently available about parasites of <jats:italic>P. falciparum<\/jats:italic> that have some degree of resistance to ACT was carried out. The data used were from transcriptomics and metabolomics studies. One mitochondrial carrier of the parasite possibly involved in the mechanisms of tolerance to oxidative stress was modeled and subjected to molecular dockings with citrate and oxoglutarate. An increase in glutathione production was detected, changing the direction of the flux of metabolites in the tricarboxylic acid cycle and boosting the glucose consumed. The models of the mitochondrial carrier, called PfCOCP, show that it may be important in transporting citrate and oxoglutarate from the mitochondrial matrix to the cytosol. If so, it may allow the parasite to tolerate the oxidative stress produced by artemisinin. This <jats:italic>in-silico<\/jats:italic> analysis shows that <jats:italic>P. falciparum<\/jats:italic> may tolerate artemisinin\u2019s oxidative stress through metabolic changes not reported before, showing the need for further experimental research on the many metabolic aspects linked to this phenotype.<\/jats:p>","DOI":"10.3389\/fpara.2024.1461641","type":"journal-article","created":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T05:28:07Z","timestamp":1725427687000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Metabolic changes that allow Plasmodium falciparum artemisinin-resistant parasites to tolerate oxidative stress"],"prefix":"10.3389","volume":"3","author":[{"given":"Alejandro David","family":"Bonive-Boscan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9ctor","family":"Acosta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ascanio","family":"Rojas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,9,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1038\/nature12876","article-title":"A molecular marker of artemisinin-resistant Plasmodium falciparum malaria","volume":"505","author":"Ariey","year":"2014","journal-title":"Nature."},{"key":"B2","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1038\/s41586-022-04475-w","article-title":"A non-canonical tricarboxylic acid cycle underlies cellular identity","volume":"603","author":"Arnold","year":"2022","journal-title":"Nature."},{"key":"B3","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1056\/NEJMoa1314981","article-title":"Spread of artemisinin resistance in Plasmodium falciparum malaria","volume":"371","author":"Ashley","year":"2014","journal-title":"N. 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