The Mitochondrial Disulfide Relay System: Roles in Oxidative Protein Folding and Beyond

Manuel Fischer,Jan Riemer

doi:10.1155/2013/742923

Abstract

Disulfide bond formation drives protein import of most proteins of the mitochondrial intermembrane space (IMS). The main components of this disulfide relay machinery are the oxidoreductase Mia40 and the sulfhydryl oxidase Erv1/ALR. Their precise functions have been elucidated in molecular detail for the yeast and human enzymes in vitro and in intact cells. However, we still lack knowledge on how Mia40 and Erv1/ALR impact cellular and organism physiology and whether they have functions beyond their role in disulfide bond formation. Here we summarize the principles of oxidation-dependent protein import mediated by the mitochondrial disulfide relay. We proceed by discussing recently described functions of Mia40 in the hypoxia response and of ALR in influencing mitochondrial morphology and its importance for tissue development and embryogenesis. We also include a discussion of the still mysterious function of Erv1/ALR in liver regeneration.

Highlights

Because almost all proteins in eukaryotic cells are synthesized by cytosolic ribosomes, protein translocation across membranes is critical for organelle biogenesis
We summarize the principles of oxidation-dependent protein import mediated by the mitochondrial disulfide relay
A similar mechanism is employed for protein import into the mitochondrial intermembrane space (IMS)

Summary

Manuel Fischer and Jan Riemer

Cellular Biochemistry, University of Kaiserslautern, Erwin-Schrodinger Straße 13, 67663 Kaiserslautern, Germany. Disulfide bond formation drives protein import of most proteins of the mitochondrial intermembrane space (IMS). The main components of this disulfide relay machinery are the oxidoreductase Mia and the sulfhydryl oxidase Erv1/ALR. Their precise functions have been elucidated in molecular detail for the yeast and human enzymes in vitro and in intact cells. We still lack knowledge on how Mia and Erv1/ALR impact cellular and organism physiology and whether they have functions beyond their role in disulfide bond formation. We proceed by discussing recently described functions of Mia in the hypoxia response and of ALR in influencing mitochondrial morphology and its importance for tissue development and embryogenesis. We include a discussion of the still mysterious function of Erv1/ALR in liver regeneration

Introduction

Disulfide Relay

Cytochrome c oxidase

Cyt c

Fragmented mitochondria

Transcription factor