Open AccessThe mitochondrial intermembrane space: the most constricted mitochondrial sub-compartment with the largest variety of protein import pathways
Author(s) -
Ruairidh Edwards,
Ross Eaglesfield,
Kostas Tokatlidis
Publication year - 2021
Publication title -
open biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.078
H-Index - 53
ISSN - 2046-2441
DOI - 10.1098/rsob.210002
Subject(s) - intermembrane space , biology , mitochondrial intermembrane space , compartment (ship) , translocase of the inner membrane , microbiology and biotechnology , mitochondrion , mitochondrial carrier , inner membrane , inner mitochondrial membrane , transport protein , mitochondrial matrix , mitochondrial membrane transport protein , biochemistry , bacterial outer membrane , cytosol , gene , enzyme , oceanography , escherichia coli , geology
The mitochondrial intermembrane space (IMS) is the most constricted sub-mitochondrial compartment, housing only about 5% of the mitochondrial proteome, and yet is endowed with the largest variability of protein import mechanisms. In this review, we summarize our current knowledge of the major IMS import pathway based on the oxidative protein folding pathway and discuss the stunning variability of other IMS protein import pathways. As IMS-localized proteins only have to cross the outer mitochondrial membrane, they do not require energy sources like ATP hydrolysis in the mitochondrial matrix or the inner membrane electrochemical potential which are critical for import into the matrix or insertion into the inner membrane. We also explore several atypical IMS import pathways that are still not very well understood and are guided by poorly defined or completely unknown targeting peptides. Importantly, many of the IMS proteins are linked to several human diseases, and it is therefore crucial to understand how they reach their normal site of function in the IMS. In the final part of this review, we discuss current understanding of how such IMS protein underpin a large spectrum of human disorders.