Elucidating the mitochondrial proteome of Toxoplasma gondii reveals the presence of a divergent cytochrome c oxidase

  1. Azadeh Seidi
  2. Linden S Muellner-Wong
  3. Esther Rajendran
  4. Edwin T Tjhin
  5. Laura Dagley
  6. Vincent YT Aw
  7. Pierre Faou
  8. Andrew I Webb
  9. Christopher J Tonkin
  10. Giel G van Dooren  Is a corresponding author
  1. Australian National University, Australia
  2. The Walter and Eliza Hall Institute of Medical Research, Australia
  3. La Trobe University, Australia

Abstract

The mitochondrion of apicomplexan parasites is critical for parasite survival, although the full complement of proteins that localize to this organelle has not been defined. Here we undertake two independent approaches to elucidate the mitochondrial proteome of the apicomplexan Toxoplasma gondii. We identify approximately 400 mitochondrial proteins, many of which lack homologs in the animals that these parasites infect, and most of which are important for parasite growth. We demonstrate that one such protein, termed TgApiCox25, is an important component of the parasite cytochrome c oxidase (COX) complex. We identify numerous other apicomplexan-specific components of COX, and conclude that apicomplexan COX, and apicomplexan mitochondria more generally, differ substantially in their protein composition from the hosts they infect. Our study highlights the diversity that exists in mitochondrial proteomes across the eukaryotic domain of life, and provides a foundation for defining unique aspects of mitochondrial biology in an important phylum of parasites.

Data availability

Mitochondrial proteomics data is available in on the ToxoDB website (http://toxodb.org).

The following data sets were generated

Article and author information

Author details

  1. Azadeh Seidi

    Research School of Biology, Australian National University, Canberra, Australia
    Competing interests
    The authors declare that no competing interests exist.
  2. Linden S Muellner-Wong

    Research School of Biology, Australian National University, Canberra, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0348-6408
  3. Esther Rajendran

    Research School of Biology, Australian National University, Canberra, Australia
    Competing interests
    The authors declare that no competing interests exist.
  4. Edwin T Tjhin

    Research School of Biology, Australian National University, Canberra, Australia
    Competing interests
    The authors declare that no competing interests exist.
  5. Laura Dagley

    The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
    Competing interests
    The authors declare that no competing interests exist.
  6. Vincent YT Aw

    Research School of Biology, Australian National University, Canberra, Australia
    Competing interests
    The authors declare that no competing interests exist.
  7. Pierre Faou

    Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  8. Andrew I Webb

    The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
    Competing interests
    The authors declare that no competing interests exist.
  9. Christopher J Tonkin

    The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
    Competing interests
    The authors declare that no competing interests exist.
  10. Giel G van Dooren

    Research School of Biology, Australian National University, Canberra, Australia
    For correspondence
    giel.vandooren@anu.edu.au
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2455-9821

Funding

Australian Research Council (DP110103144)

  • Giel G van Dooren

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Dominique Soldati-Favre, University of Geneva, Switzerland

Version history

  1. Received: May 6, 2018
  2. Accepted: September 9, 2018
  3. Accepted Manuscript published: September 11, 2018 (version 1)
  4. Version of Record published: September 25, 2018 (version 2)

Copyright

© 2018, Seidi et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 3,911
    views
  • 536
    downloads
  • 84
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Azadeh Seidi
  2. Linden S Muellner-Wong
  3. Esther Rajendran
  4. Edwin T Tjhin
  5. Laura Dagley
  6. Vincent YT Aw
  7. Pierre Faou
  8. Andrew I Webb
  9. Christopher J Tonkin
  10. Giel G van Dooren
(2018)
Elucidating the mitochondrial proteome of Toxoplasma gondii reveals the presence of a divergent cytochrome c oxidase
eLife 7:e38131.
https://doi.org/10.7554/eLife.38131

Share this article

https://doi.org/10.7554/eLife.38131

Further reading

    1. Epidemiology and Global Health
    2. Microbiology and Infectious Disease
    Clara Akpan
    Insight

    Systematically tracking and analysing reproductive loss in livestock helps with efforts to safeguard the health and productivity of food animals by identifying causes and high-risk areas.

    1. Microbiology and Infectious Disease
    Hina Khan, Partha Paul ... Dibyendu Sarkar
    Research Article

    Survival of Mycobacterium tuberculosis within the host macrophages requires the bacterial virulence regulator PhoP, but the underlying reason remains unknown. 3′,5′-Cyclic adenosine monophosphate (cAMP) is one of the most widely used second messengers, which impacts a wide range of cellular responses in microbial pathogens including M. tuberculosis. Herein, we hypothesized that intra-bacterial cAMP level could be controlled by PhoP since this major regulator plays a key role in bacterial responses against numerous stress conditions. A transcriptomic analysis reveals that PhoP functions as a repressor of cAMP-specific phosphodiesterase (PDE) Rv0805, which hydrolyzes cAMP. In keeping with these results, we find specific recruitment of the regulator within the promoter region of rv0805 PDE, and absence of phoP or ectopic expression of rv0805 independently accounts for elevated PDE synthesis, leading to the depletion of intra-bacterial cAMP level. Thus, genetic manipulation to inactivate PhoP-rv0805-cAMP pathway decreases cAMP level, stress tolerance, and intracellular survival of the bacillus.