Two ancient membrane pores mediate mitochondrial-nucleus membrane contact sites

Ovciarikova, J. et al. (2024) Two ancient membrane pores mediate mitochondrial-nucleus membrane contact sites. Journal of Cell Biology, 223(4), e202304075. (doi: 10.1083/jcb.202304075) (PMID:38456969)

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Abstract

Coordination between nucleus and mitochondria is essential for cell survival, and thus numerous communication routes have been established between these two organelles over eukaryotic cell evolution. One route for organelle communication is via membrane contact sites, functional appositions formed by molecular tethers. We describe a novel nuclear-mitochondrial membrane contact site in the protozoan Toxoplasma gondii. We have identified specific contacts occurring at the nuclear pore and demonstrated an interaction between components of the nuclear pore and the mitochondrial protein translocon, highlighting them as molecular tethers. Genetic disruption of the nuclear pore or the TOM translocon components, TgNup503 or TgTom40, respectively, result in contact site reduction, supporting their potential involvement in this tether. TgNup503 depletion further leads to specific mitochondrial morphology and functional defects, supporting a role for nuclear-mitochondrial contacts in mediating their communication. The discovery of a contact formed through interaction between two ancient mitochondrial and nuclear complexes sets the ground for better understanding of mitochondrial-nuclear crosstalk in eukaryotes.

Item Type:Articles
Additional Information:Funders: Wellcome Trust, grant 217173/Z/19/Z; and the Biotechnology and Biological Sciences Research Council, grant BB/N003675/1 to L. Sheiner; French National Research Agency, grant number ANR-13-JSV3-0006-01 to M. Gissot. E.S. Martins-Duarte received support from Pró-Reitoria de Pesquisa-UFMG and Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (408964/2018-9). S. Shikha is funded by the Swiss National Foundation Early Postdoc Mobility fellowship.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Ovciarikova, Miss Jana and Lacombe, Alice and MacLean, Dr Andrew and Hussain, Dr Wasim and Sheiner, Professor Lilach and Lemgruber Soares, Dr Leandro
Creator Roles:
Ovciarikova, J.Data curation, Formal analysis, Investigation, Methodology, Supervision, Validation, Visualization, Writing – review and editing
Lacombe, A.Investigation
Hussain, W.Investigation
MacLean, A.Investigation
Lemgruber, L.Formal analysis, Investigation, Methodology, Visualization
Sheiner, L.Conceptualization, Funding acquisition, Project administration, Supervision, Investigation, Writing – original draft, Writing – review and editing
Authors: Ovciarikova, J., Shikha, S., Lacombe, A., Courjol, F., McCrone, R., Hussain, W., MacLean, A., Lemgruber, L., Martins-Duarte, E. S., Gissot, M., and Sheiner, L.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Journal of Cell Biology
Publisher:Rockefeller University Press
ISSN:0021-9525
ISSN (Online):1540-8140
Published Online:08 March 2024
Copyright Holders:Copyright © 2024 Ovciarikova et al.
First Published:First published in Journal of Cell Biology 223(4):e202304075
Publisher Policy:Reproduced under a Creative Commons license

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
307056Lost in translation. A study of the divergent mitochondrial translation pathway of the parasite Toxoplasma gondiiLilach SheinerWellcome Trust (WELLCOTR)217173/Z/19/ZMVLS - Research Facilities
172187Dissection of the unusual mitochondrial tRNA import translocon of Toxoplasma gondiiLilach SheinerBiotechnology and Biological Sciences Research Council (BBSRC)BB/N003675/1School of Infection & Immunity