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Among eukaryotes, alternative oxidases have dispersed distribution and are found in plants, fungi, and protists, including <jats:italic>Naegleria<\/jats:italic> ssp. <jats:italic>Naegleria<\/jats:italic> species are free\u2010living unicellular amoeboflagellates and include the pathogenic species of <jats:italic>N<\/jats:italic>.\u00a0<jats:italic>fowleri<\/jats:italic>, the so\u2010called \u201cbrain\u2010eating amoeba.\u201d Using a multidisciplinary approach, we aimed to understand the evolution, localization, and function of AOX and the role that plays in <jats:italic>Naegleria<\/jats:italic>'s biology. Our analyses suggest that AOX was present in last common ancestor of the genus and structure prediction showed that all functional residues are also present in <jats:italic>Naegleria<\/jats:italic> species. Using cellular and biochemical techniques, we also functionally characterize <jats:italic>N<\/jats:italic>.\u00a0<jats:italic>gruberi<\/jats:italic>'s AOX in its mitochondria, and we demonstrate that its inactivation affects its proliferation. Consequently, we discuss the benefits of the presence of this protein in <jats:italic>Naegleria<\/jats:italic> species, along with its potential pathogenicity role in <jats:italic>N<\/jats:italic>.\u00a0<jats:italic>fowleri<\/jats:italic>. We predict that our findings will spearhead new explorations to understand the cell biology, metabolism, and evolution of <jats:italic>Naegleria<\/jats:italic> and other free\u2010living relatives.<\/jats:p>","DOI":"10.1111\/jeu.12908","type":"journal-article","created":{"date-parts":[[2022,3,24]],"date-time":"2022-03-24T21:09:35Z","timestamp":1648156175000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Localization and functional characterization of the alternative oxidase in <i>Naegleria<\/i>"],"prefix":"10.1111","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8527-7719","authenticated-orcid":false,"given":"Diego","family":"Cantoni","sequence":"first","affiliation":[{"name":"Laboratory of Molecular &amp; Evolutionary Parasitology, RAPID Group School of Biosciences University of Kent  Canterbury 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