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International Journal of Cell Biology
Volume 2013, Article ID 742923, 12 pages
Review Article

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

Cellular Biochemistry, University of Kaiserslautern, Erwin-Schrödinger Straße 13, 67663 Kaiserslautern, Germany

Received 9 July 2013; Accepted 1 October 2013

Academic Editor: Agnès Delaunay-Moisan

Copyright © 2013 Manuel Fischer and Jan Riemer. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.