The biogenesis of mitochondrial intermembrane space proteins

Edwards, R., Gerlich, S. and Tokatlidis, K. (2020) The biogenesis of mitochondrial intermembrane space proteins. Biological Chemistry, 401(6-7), pp. 737-747. (doi: 10.1515/hsz-2020-0114) (PMID:32061164)

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The mitochondrial intermembrane space (IMS) houses a large spectrum of proteins with distinct and critical functions. Protein import into this mitochondrial sub-compartment is underpinned by an intriguing variety of pathways, many of which are still poorly understood. The constricted volume of the IMS and the topological segregation by the inner membrane cristae into a bulk area surrounded by the boundary inner membrane and the lumen within the cristae is an important factor that adds to the complexity of the protein import, folding and assembly processes. We discuss the main import pathways into the IMS, but also how IMS proteins are degraded or even retro-translocated to the cytosol in an integrated network of interactions that is necessary to maintain a healthy balance of IMS proteins under physiological and cellular stress conditions. We conclude this review by highlighting new and exciting perspectives in this area with a view to develop a better understanding of yet unknown, likely unconventional import pathways, how presequence-less proteins can be targeted and the basis for dual localisation in the IMS and the cytosol. Such knowledge is critical to understanding the dynamic changes of the IMS proteome in response to stress, and particularly important for maintaining optimal mitochondrial fitness.

Item Type:Articles
Keywords:Clinical biochemistry, biochemistry, molecular biology.
Glasgow Author(s) Enlighten ID:Gerlich, Miss Sarah and Edwards, Mr Ruairidh and Tokatlidis, Professor Kostas
Authors: Edwards, R., Gerlich, S., and Tokatlidis, K.
College/School:College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
Journal Name:Biological Chemistry
Publisher:De Gruyter
ISSN (Online):1437-4315
Published Online:12 March 2020
Copyright Holders:Copyright © 2020 Walter de Gruyter GmbH
First Published:First published in Biological Chemistry 401(6-7): 737-747
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
300402Mitochondria salvage via a novel antioxidant protein import pathwayKonstantinos TokatlidisBiotechnology and Biological Sciences Research Council (BBSRC)BB/R009031/1Institute of Molecular, Cell & Systems Biology
306567Mitochondrial ROS mapping and control with sub-organellar resolutionKonstantinos TokatlidisBiotechnology and Biological Sciences Research Council (BBSRC)BB/T003804/1Institute of Molecular, Cell & Systems Biology