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These cofactors cannot be scavenged or trafficked within a cell and thus must be synthesized in any subcellular compartment where they are required. We examined the FeS synthesis proteins found in the relict plastid organelle, called the apicoplast, of the human malaria parasite\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    . Using a chemical bypass method, we deleted four of the FeS pathway proteins involved in sulfur acquisition and cluster assembly and demonstrated that they are all essential for parasite survival. However, the effect that these deletions had on the apicoplast organelle differed. Deletion of the cysteine desulfurase SufS led to disruption of the apicoplast organelle and loss of the organellar genome, whereas the other deletions did not affect organelle maintenance. Ultimately, we discovered that the requirement of SufS for organelle maintenance is not driven by its role in FeS biosynthesis, but rather, by its function in generating sulfur for use by MnmA, a tRNA modifying enzyme that we localized to the apicoplast. Complementation of MnmA and SufS activity with a bacterial MnmA and its cognate cysteine desulfurase strongly suggests that the parasite SufS provides sulfur for both FeS biosynthesis and tRNA modification in the apicoplast. The dual role of parasite SufS is likely to be found in other plastid-containing organisms and highlights the central role of this enzyme in plastid biology.\n                  <\/jats:p>","DOI":"10.7554\/elife.84491","type":"journal-article","created":{"date-parts":[[2023,5,11]],"date-time":"2023-05-11T06:15:19Z","timestamp":1683785719000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.84491","source":"Crossref","is-referenced-by-count":24,"title":["The Plasmodium falciparum apicoplast cysteine desulfurase provides sulfur for both iron-sulfur cluster assembly and tRNA modification"],"prefix":"10.7554","volume":"12","author":[{"given":"Russell P","family":"Swift","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00za53h95","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Microbiology and Immunology, Johns Hopkins University","place":["Baltimore, United States"]},{"name":"The Johns Hopkins Malaria Research Institute","place":["Baltimore, 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