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In mammals, acetyl-CoA transporter 1 (AT1, also known as SLC33A1) facilitates the flux of cytosolic acetyl-CoA into the endoplasmic reticulum (ER), enabling the acetylation of proteins of the secretory pathway, in concert with the activity of dedicated acetyltransferases such as NAT8. However, the involvement of the ER acetyl-CoA pool in acetylation of ER-transiting proteins in Apicomplexa is unknown. Here, we identified homologs of AT1 and NAT8 in Toxoplasma gondii and Plasmodium berghei parasites. Proteome-wide analyses revealed widespread N-terminal acetylation of secreted proteins in both species. Such extensive acetylation of N-terminally processed proteins has not been observed previously in any other organism. Deletion of AT1 homologs in both T. gondii and P. berghei resulted in considerable reductions in parasite fitness. In P. berghei, AT1 was found to be important for growth of asexual blood stages, production of female gametocytes and male gametocytogenesis, implying its requirement for parasite transmission. In the absence of AT1, lysine acetylation and N-terminal acetylation in T. gondii remained globally unaltered, suggesting an uncoupling between the role of AT1 in development and active acetylation occurring along the secretory pathway.<\/jats:p>","DOI":"10.1242\/jcs.259811","type":"journal-article","created":{"date-parts":[[2022,5,27]],"date-time":"2022-05-27T09:33:24Z","timestamp":1653644004000},"source":"Crossref","is-referenced-by-count":14,"title":["N-acetylation of secreted proteins in Apicomplexa is widespread and is independent of the ER acetyl-CoA transporter AT1"],"prefix":"10.1242","volume":"135","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5271-5089","authenticated-orcid":false,"given":"Mary Akinyi","family":"Nyonda","sequence":"first","affiliation":[{"name":"University of Geneva 1 Department of Microbiology and Molecular Medicine , , Geneva 1211 , Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5265-3917","authenticated-orcid":false,"given":"Jean-Baptiste","family":"Boyer","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, CEA, CNRS, Institute for Intergrative Biology of the Cell (I2BC) 2 , 91198 Gif-sur-Yvette , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3515-0055","authenticated-orcid":false,"given":"Lucid","family":"Belmudes","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Grenoble Alpes, INSERM, CEA, UMR BioSant\u00e9 U1292, CNRS, CEA, FR2048 3 , 38000 Grenoble , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7936-4442","authenticated-orcid":false,"given":"Aarti","family":"Krishnan","sequence":"additional","affiliation":[{"name":"University of Geneva 1 Department of Microbiology and Molecular Medicine , , Geneva 1211 , Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9705-1389","authenticated-orcid":false,"given":"Paco","family":"Pino","sequence":"additional","affiliation":[{"name":"University of Geneva 1 Department of Microbiology and Molecular Medicine , , Geneva 1211 , Switzerland"},{"name":"ExcellGene SA 4 , CH1870 Monthey , Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3896-6196","authenticated-orcid":false,"given":"Yohann","family":"Cout\u00e9","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Grenoble Alpes, INSERM, CEA, UMR BioSant\u00e9 U1292, CNRS, CEA, FR2048 3 , 38000 Grenoble , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3911-5537","authenticated-orcid":false,"given":"Mathieu","family":"Brochet","sequence":"additional","affiliation":[{"name":"University of Geneva 1 Department of Microbiology and Molecular Medicine , , Geneva 1211 , Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5642-8637","authenticated-orcid":false,"given":"Thierry","family":"Meinnel","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, CEA, CNRS, Institute for Intergrative Biology of the Cell (I2BC) 2 , 91198 Gif-sur-Yvette , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4156-2109","authenticated-orcid":false,"given":"Dominique","family":"Soldati-Favre","sequence":"additional","affiliation":[{"name":"University of Geneva 1 Department of Microbiology and Molecular Medicine , , Geneva 1211 , Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7475-1558","authenticated-orcid":false,"given":"Carmela","family":"Giglione","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, CEA, CNRS, Institute for Intergrative Biology of the Cell (I2BC) 2 , 91198 Gif-sur-Yvette , France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2022,8,5]]},"reference":[{"key":"2022080509341422100_JCS259811C1","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1016\/j.tibs.2016.07.005","article-title":"First things first: vital protein marks by N-terminal acetyltransferases","volume":"41","author":"Aksnes","year":"2016","journal-title":"Trends Biochem. 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