Localization and functional characterization of the alternative oxidase in Naegleria

Cantoni, D. et al. (2022) Localization and functional characterization of the alternative oxidase in Naegleria. Journal of Eukaryotic Microbiology, 69(4), e12908. (doi: 10.1111/jeu.12908) (PMID:35322502) (PMCID:PMC9540462)

Abstract

The alternative oxidase (AOX) is a protein involved in supporting enzymatic reactions of the Krebs cycle in instances when the canonical (cytochrome-mediated) respiratory chain has been inhibited, while allowing for the maintenance of cell growth and necessary metabolic processes for survival. Among eukaryotes, alternative oxidases have dispersed distribution and are found in plants, fungi, and protists, including Naegleria ssp. Naegleria species are free-living unicellular amoeboflagellates and include the pathogenic species of N. fowleri, the so-called “brain-eating amoeba.” Using a multidisciplinary approach, we aimed to understand the evolution, localization, and function of AOX and the role that plays in Naegleria'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 Naegleria species. Using cellular and biochemical techniques, we also functionally characterize N. gruberi'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 Naegleria species, along with its potential pathogenicity role in N. fowleri. We predict that our findings will spearhead new explorations to understand the cell biology, metabolism, and evolution of Naegleria and other free-living relatives.

• Item Type: Articles
• Additional Information: Alfonso Martín Escudero Foundation; Gordon and Betty Moore Foundation; Biotechnology and Biological Sciences Research Council, Grant/Award Number: BB/M009971/1
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Cantoni, Dr Diego
• Authors: Cantoni, D., Osborne, A., Taib, N., Thompson, G., Martín‐Escolano, R., Kazana, E., Edrich, E., Brown, I. R., Gribaldo, S., Gourlay, C. W., and Tsaousis, A. D.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Journal of Eukaryotic Microbiology
• Publisher: Wiley
• ISSN: 1066-5234
• ISSN (Online): 1550-7408
• Published Online: 03 May 2022
• Copyright Holders: Copyright: © 2022 The Authors
• First Published: First published in Journal of Eukaryotic Microbiology 69(4): e12908
• Publisher Policy: Reproduced under a Creative Commons licence