{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T12:08:41Z","timestamp":1789474121651,"version":"build-2803163510"},"reference-count":48,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministerio de Ciencia e Innovaci\u00f3n from Spain","award":["PID2023-147765OB-C21, -C22"],"award-info":[{"award-number":["PID2023-147765OB-C21, -C22"]}]},{"award":["PID2023-147765OB-C21, -C22"],"award-info":[{"award-number":["PID2023-147765OB-C21, -C22"]}],"id":[{"id":"https:\/\/ror.org\/05r0vyz12","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Fundaci\u00f3n Roviralta"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>The translocase of the outer membrane (TOM) complex is the primary entry gate for nucleus-encoded mitochondrial proteins and is conserved across eukaryotes; however, parasitic protists exhibit remarkable adaptations. This review synthesizes current knowledge on the composition, structure, and function of TOM and related import systems in apicomplexans, kinetoplastids, and anaerobic protists with reduced mitochondrion-related organelles (MROs). We highlight major evolutionary innovations, including the bacterial-origin ATOM complex in trypanosomes\u2014comprising core channel ATOM40, receptors ATOM46\/69, structural subunit ATOM19, and multifunctional pATOM36 linking protein import to mitochondrial DNA inheritance\u2014alongside lineage-specific receptors such as Tom60 in Entamoeba histolytica and extreme reductive streamlining in microsporidian mitosomes. Beyond its canonical role in biogenesis, we explore how parasites co-opt the host TOM complex for intracellular survival and how the import machinery integrates with broader cellular processes, including immune signaling, stress responses, and organelle dynamics. Notably, the essential nature of these adapted systems, coupled with their significant divergence from host machinery, highlights their potential as targets for developing novel therapeutic strategies against major parasitic diseases. This work underscores that understanding the diversity of mitochondrial protein import pathways not only provides insights into eukaryotic evolution but may also open new avenues for the development of antiparasitic drugs.<\/jats:p>","DOI":"10.3390\/ijms27188205","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T11:57:34Z","timestamp":1789473454000},"page":"8205","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evolution and Adaptation of the Mitochondrial Protein Import Machinery in Parasitic Protists: Beyond the Canonical TOM Complex"],"prefix":"10.3390","volume":"27","author":[{"given":"Enayat","family":"Anvari","sequence":"first","affiliation":[{"name":"Department of Physiology, School of Medicine, Ilam University of Medical Science, Ilam, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gholamreza","family":"Daryabor","sequence":"additional","affiliation":[{"name":"Autoimmune Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5520-1211","authenticated-orcid":false,"given":"Amin","family":"Sedigh","sequence":"additional","affiliation":[{"name":"Molecular Medicine Research Center, Khomein University of Medical Sciences, Khomein, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4675-7274","authenticated-orcid":false,"given":"Sajad","family":"Rashidi","sequence":"additional","affiliation":[{"name":"Molecular Medicine Research Center, Khomein University of Medical Sciences, Khomein, Iran"},{"name":"Department of Basic Sciences, Khomein University of Medical Sciences, Khomein, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2193-7316","authenticated-orcid":false,"given":"Paul","family":"Nguewa","sequence":"additional","affiliation":[{"name":"Areas of Microbiology and Parasitology, Department of Molecular Biology,  University of Navarra, IdiSNA (Navarra Institute for Health Research), c\/Irunlarrea 1, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e190022","DOI":"10.2142\/biophysico.bppb-v19.0022","article-title":"Structural overview of the translocase of the mitochondrial outer membrane complex","volume":"19","author":"Araiso","year":"2022","journal-title":"Biophys. 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