Protein Quality Control at the Mitochondrial Surface

Fabian Den Brave,Thomas Becker,Arushi Gupta

doi:10.3389/fcell.2021.795685

Fabian Den Brave, Thomas Becker + Show 1 more

Open Access

https://doi.org/10.3389/fcell.2021.795685

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Abstract

Mitochondria contain two membranes, the outer and inner membrane. The outer membrane fulfills crucial functions for the communication of mitochondria with the cellular environment like exchange of lipids via organelle contact sites, the transport of metabolites and the formation of a signaling platform in apoptosis and innate immunity. The translocase of the outer membrane (TOM complex) forms the entry gate for the vast majority of precursor proteins that are produced on cytosolic ribosomes. Surveillance of the functionality of outer membrane proteins is critical for mitochondrial functions and biogenesis. Quality control mechanisms remove defective and mistargeted proteins from the outer membrane as well as precursor proteins that clog the TOM complex. Selective degradation of single proteins is also an important mode to regulate mitochondrial dynamics and initiation of mitophagy pathways. Whereas inner mitochondrial compartments are equipped with specific proteases, the ubiquitin-proteasome system is a central player in protein surveillance on the mitochondrial surface. In this review, we summarize our current knowledge about the molecular mechanisms that govern quality control of proteins at the outer mitochondrial membrane.

Highlights

Mitochondria are known as the powerhouse of the cell since they produce the bulk of energy for cellular processes
We summarize here our current knowledge about surveillance of proteins on the mitochondrial surface
It was reported that outer membrane proteins like Om45 and Tom22 that expose a soluble domain towards the intermembrane space can be degraded by the hexameric AAA-protease Yme1 (Wu et al, 2018)

Summary

Introduction

Mitochondria are known as the powerhouse of the cell since they produce the bulk of energy for cellular processes. The majority of these precursor proteins is not transported via the TOM channel, but instead transferred to the MIM complex on the cytosolic side of the outer membrane. The mitochondrial protein translocation-associated degradation (mitoTAD) pathway continuously monitors the TOM complex to prevent clogging of the translocation channel with precursor proteins (Figure 2; Martensson et al, 2019).

Results

Conclusion