IMC10 and LMF1 mediate mitochondrial morphology through mitochondrion–pellicle contact sites in Toxoplasma gondii

The single mitochondrion of Toxoplasma gondii is highly dynamic, being predominantly in a peripherally distributed lasso-shape in intracellular parasites and collapsed in extracellular parasites. The peripheral positioning of the mitochondrion is associated with apparent contacts between the mitocho...

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Autores principales: Oliveira Souza, Rodolpho Ornitz, Jacobs, Kylie N., Back, Peter S., Bradley, Peter J., Arrizabalaga, Gustavo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9845740/
https://www.ncbi.nlm.nih.gov/pubmed/36314270
http://dx.doi.org/10.1242/jcs.260083
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author Oliveira Souza, Rodolpho Ornitz
Jacobs, Kylie N.
Back, Peter S.
Bradley, Peter J.
Arrizabalaga, Gustavo
author_facet Oliveira Souza, Rodolpho Ornitz
Jacobs, Kylie N.
Back, Peter S.
Bradley, Peter J.
Arrizabalaga, Gustavo
author_sort Oliveira Souza, Rodolpho Ornitz
collection PubMed
description The single mitochondrion of Toxoplasma gondii is highly dynamic, being predominantly in a peripherally distributed lasso-shape in intracellular parasites and collapsed in extracellular parasites. The peripheral positioning of the mitochondrion is associated with apparent contacts between the mitochondrion membrane and the parasite pellicle. The outer mitochondrial membrane-associated protein LMF1 is critical for the correct positioning of the mitochondrion. Intracellular parasites lacking LMF1 fail to form the lasso-shaped mitochondrion. To identify other proteins that tether the mitochondrion of the parasite to the pellicle, we performed a yeast two-hybrid screen for LMF1 interactors. We identified 70 putative interactors localized in different cellular compartments, such as the apical end of the parasite, mitochondrial membrane and the inner membrane complex (IMC), including with the pellicle protein IMC10. Using protein–protein interaction assays, we confirmed the interaction of LMF1 with IMC10. Conditional knockdown of IMC10 does not affect parasite viability but severely affects mitochondrial morphology in intracellular parasites and mitochondrial distribution to the daughter cells during division. In effect, IMC10 knockdown phenocopies disruption of LMF1, suggesting that these two proteins define a novel membrane tether between the mitochondrion and the IMC in Toxoplasma. This article has an associated First Person interview with the first author of the paper.
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spelling pubmed-98457402023-02-06 IMC10 and LMF1 mediate mitochondrial morphology through mitochondrion–pellicle contact sites in Toxoplasma gondii Oliveira Souza, Rodolpho Ornitz Jacobs, Kylie N. Back, Peter S. Bradley, Peter J. Arrizabalaga, Gustavo J Cell Sci Research Article The single mitochondrion of Toxoplasma gondii is highly dynamic, being predominantly in a peripherally distributed lasso-shape in intracellular parasites and collapsed in extracellular parasites. The peripheral positioning of the mitochondrion is associated with apparent contacts between the mitochondrion membrane and the parasite pellicle. The outer mitochondrial membrane-associated protein LMF1 is critical for the correct positioning of the mitochondrion. Intracellular parasites lacking LMF1 fail to form the lasso-shaped mitochondrion. To identify other proteins that tether the mitochondrion of the parasite to the pellicle, we performed a yeast two-hybrid screen for LMF1 interactors. We identified 70 putative interactors localized in different cellular compartments, such as the apical end of the parasite, mitochondrial membrane and the inner membrane complex (IMC), including with the pellicle protein IMC10. Using protein–protein interaction assays, we confirmed the interaction of LMF1 with IMC10. Conditional knockdown of IMC10 does not affect parasite viability but severely affects mitochondrial morphology in intracellular parasites and mitochondrial distribution to the daughter cells during division. In effect, IMC10 knockdown phenocopies disruption of LMF1, suggesting that these two proteins define a novel membrane tether between the mitochondrion and the IMC in Toxoplasma. This article has an associated First Person interview with the first author of the paper. The Company of Biologists Ltd 2022-11-15 /pmc/articles/PMC9845740/ /pubmed/36314270 http://dx.doi.org/10.1242/jcs.260083 Text en © 2022. Published by The Company of Biologists Ltd https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article
Oliveira Souza, Rodolpho Ornitz
Jacobs, Kylie N.
Back, Peter S.
Bradley, Peter J.
Arrizabalaga, Gustavo
IMC10 and LMF1 mediate mitochondrial morphology through mitochondrion–pellicle contact sites in Toxoplasma gondii
title IMC10 and LMF1 mediate mitochondrial morphology through mitochondrion–pellicle contact sites in Toxoplasma gondii
title_full IMC10 and LMF1 mediate mitochondrial morphology through mitochondrion–pellicle contact sites in Toxoplasma gondii
title_fullStr IMC10 and LMF1 mediate mitochondrial morphology through mitochondrion–pellicle contact sites in Toxoplasma gondii
title_full_unstemmed IMC10 and LMF1 mediate mitochondrial morphology through mitochondrion–pellicle contact sites in Toxoplasma gondii
title_short IMC10 and LMF1 mediate mitochondrial morphology through mitochondrion–pellicle contact sites in Toxoplasma gondii
title_sort imc10 and lmf1 mediate mitochondrial morphology through mitochondrion–pellicle contact sites in toxoplasma gondii
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9845740/
https://www.ncbi.nlm.nih.gov/pubmed/36314270
http://dx.doi.org/10.1242/jcs.260083
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