An essential role for an Fe-S cluster protein in the cytochrome c oxidase complex of Toxoplasma parasites

Rachel A Leonard; Yuan Tian; Feng Tan; Giel G van Dooren; Jenni A Hayward

doi:10.1371/journal.ppat.1011430

An essential role for an Fe-S cluster protein in the cytochrome c oxidase complex of Toxoplasma parasites

PLoS Pathog. 2023 Jun 1;19(6):e1011430. doi: 10.1371/journal.ppat.1011430. eCollection 2023 Jun.

Authors

Rachel A Leonard¹, Yuan Tian², Feng Tan², Giel G van Dooren¹, Jenni A Hayward¹

Affiliations

¹ Research School of Biology, Australian National University, Canberra, Australian Capital Territory, Australia.
² Department of Parasitology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang China.

Abstract

The mitochondrial electron transport chain (ETC) of apicomplexan parasites differs considerably from the ETC of the animals that these parasites infect, and is the target of numerous anti-parasitic drugs. The cytochrome c oxidase complex (Complex IV) of the apicomplexan Toxoplasma gondii ETC is more than twice the mass and contains subunits not found in human Complex IV, including a 13 kDa protein termed TgApiCox13. TgApiCox13 is homologous to a human iron-sulfur (Fe-S) cluster-containing protein called the mitochondrial inner NEET protein (HsMiNT) which is not a component of Complex IV in humans. Here, we establish that TgApiCox13 is a critical component of Complex IV in T. gondii, required for complex activity and stability. Furthermore, we demonstrate that TgApiCox13, like its human homolog, binds two Fe-S clusters. We show that the Fe-S clusters of TgApiCox13 are critical for ETC function, having an essential role in mediating Complex IV integrity. Our study provides the first functional characterisation of an Fe-S protein in Complex IV.

Copyright: © 2023 Leonard et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Electron Transport Complex IV / metabolism
Humans
Mitochondrial Membranes / metabolism
Mitochondrial Proteins / genetics
Mitochondrial Proteins / metabolism
Parasites* / metabolism
Toxoplasma* / metabolism

Substances

Electron Transport Complex IV
Mitochondrial Proteins

Grants and funding

This work was supported by a National Health and Medical Research Council Ideas grant (GNT1182369) to GGvD, grants from the National Natural Science Foundation of China (81971962, 82172303) to FT, and an Australian Government Research Training Program Scholarship to JAH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.