The Diversity of the Mitochondrial Outer Membrane Protein Import Channels: Emerging Targets for Modulation

Abstract

The functioning of mitochondria and their biogenesis are largely based on the proper function of the mitochondrial outer membrane channels, which selectively recognise and import proteins but also transport a wide range of other molecules, including metabolites, inorganic ions and nucleic acids. To date, nine channels have been identified in the mitochondrial outer membrane of which at least half represent the mitochondrial protein import apparatus. When compared to the mitochondrial inner membrane, the presented channels are mostly constitutively open and consequently may participate in transport of different molecules and contribute to relevant changes in the outer membrane permeability based on the channel conductance. In this review, we focus on the channel structure, properties and transported molecules as well as aspects important to their modulation. This information could be used for future studies of the cellular processes mediated by these channels, mitochondrial functioning and therapies for mitochondria-linked diseases.

Bcl-2 Family Members and the Mitochondrial Import Machineries: The Roads to Death

“…The outer membrane of mitochondria contains a highly specialized protein complex implicated in protein import into the organelle called TOM for translocase of outer membrane and a more specialized complex called sorting and assembly machinery (SAM), which are responsible for nuclei-encoded proteins import within mitochondria or insertion into the mitochondrial outer membrane (MOM) ( Figure 1 ) [ 9 ]. β-Barrel proteins also exist in mammalian mitochondria such as VDAC1 and 2, SAM50, and TOM40 [ 10 ]. Both TOMs and SAMs have been implicated in both macromolecules transport and apoptosis [ 11 ].…”

A Correlation between 3′-UTR of OXA1 Gene and Yeast Mitochondrial Translation

“…Little is known about the mechanism of RNA transport into human mitochondria. However, similar to what has been observed in yeast, RNA translocation in human cells seems to require membrane potential, possibly mediated by TOM or VDAC channel, across the mitochondrial membranes [32]. Another possible translocation mechanism is through intermembrane space by the activity of polynucleotide phosphorylase (PNPase) protein [33].…”

“…An inner membrane translocation factor has not been discovered [27]. In yeast, tRNA import into mitochondria is facilitated by the translocase proteins of the outer and inner membranes, called TOM and TIM, respectively [27,32]. Little is known about the mechanism of RNA transport into human mitochondria.…”

Solute Transport through Mitochondrial Porins In Vitro and In Vivo

“…The renaturation of the expressed proteins is possible in vitro, similar to water-soluble forms of mitochondrial porins of different organisms [ 67 , 68 , 69 , 70 ], although the translation of the protein into mitochondria after synthesis in vivo at cytoplasmic ribosomes has nothing to do with the folding of the in vitro protein in non-ionic detergents. Mitochondrial porins are transported post-translationally via the Tom40 complex into the intermembrane space of mitochondria and inserted via the Tob44/Sam50 protein, a member of the Omp85 family of proteins in the mitochondrial outer membrane [ 71 , 72 , 73 ]. Heterologous expression of eukaryotic porins also allows for easy mutations of single important amino acids and the deletion of stretches of amino acids within their primary structure, which helps to study the function of these amino acids in channel gating and voltage dependence [ 68 , 74 , 75 ].…”