Differential contribution of two organelles of endosymbiotic origin to iron-sulfur cluster synthesis and overall fitness in Toxoplasma.


Journal

PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921

Informations de publication

Date de publication:
11 2021
Historique:
received: 01 09 2021
accepted: 05 11 2021
revised: 02 12 2021
pubmed: 19 11 2021
medline: 1 1 2022
entrez: 18 11 2021
Statut: epublish

Résumé

Iron-sulfur (Fe-S) clusters are one of the most ancient and ubiquitous prosthetic groups, and they are required by a variety of proteins involved in important metabolic processes. Apicomplexan parasites have inherited different plastidic and mitochondrial Fe-S clusters biosynthesis pathways through endosymbiosis. We have investigated the relative contributions of these pathways to the fitness of Toxoplasma gondii, an apicomplexan parasite causing disease in humans, by generating specific mutants. Phenotypic analysis and quantitative proteomics allowed us to highlight notable differences in these mutants. Both Fe-S cluster synthesis pathways are necessary for optimal parasite growth in vitro, but their disruption leads to markedly different fates: impairment of the plastidic pathway leads to a loss of the organelle and to parasite death, while disruption of the mitochondrial pathway trigger differentiation into a stress resistance stage. This highlights that otherwise similar biochemical pathways hosted by different sub-cellular compartments can have very different contributions to the biology of the parasites, which is something to consider when exploring novel strategies for therapeutic intervention.

Identifiants

pubmed: 34793583
doi: 10.1371/journal.ppat.1010096
pii: PPATHOGENS-D-21-01794
pmc: PMC8639094
doi:

Substances chimiques

Iron-Sulfur Proteins 0
Proteome 0
Protozoan Proteins 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

e1010096

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

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Auteurs

Sarah Pamukcu (S)

LPHI, Univ Montpellier, CNRS, Montpellier, France.

Aude Cerutti (A)

LPHI, Univ Montpellier, CNRS, Montpellier, France.

Yann Bordat (Y)

LPHI, Univ Montpellier, CNRS, Montpellier, France.

Sonia Hem (S)

BPMP, Univ Montpellier, CNRS, INRAE, Institut Agro, Montpellier, France.

Valérie Rofidal (V)

BPMP, Univ Montpellier, CNRS, INRAE, Institut Agro, Montpellier, France.

Sébastien Besteiro (S)

LPHI, Univ Montpellier, CNRS, INSERM, Montpellier, France.

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