Protein import by the mitochondrial disulfide relay in higher eukaryotes

  • 1 Institute for Biochemistry, Redox Biochemistry, University of Cologne, Zülpicher Str. 47a/R. 3.49, D-50674 Cologne, Germany
  • 2 Department of Chemistry, Institute for Biochemistry, Redox Biochemistry, University of Cologne, and Cologne Excellence Cluster on Cellular Stress Response in Aging-Associated Diseases, Zülpicher Str. 47a/R. 3.49, D-50674 Cologne, Germany
Yannik Finger
  • Institute for Biochemistry, Redox Biochemistry, University of Cologne, Zülpicher Str. 47a/R. 3.49, D-50674 Cologne, Germany
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and Jan RiemerORCID iD: https://orcid.org/0000-0002-7574-8457
  • Corresponding author
  • Department of Chemistry, Institute for Biochemistry, Redox Biochemistry, University of Cologne, and Cologne Excellence Cluster on Cellular Stress Response in Aging-Associated Diseases, Zülpicher Str. 47a/R. 3.49, D-50674 Cologne, Germany
  • orcid.org/0000-0002-7574-8457
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Abstract

The proteome of the mitochondrial intermembrane space (IMS) contains more than 100 proteins, all of which are synthesized on cytosolic ribosomes and consequently need to be imported by dedicated machineries. The mitochondrial disulfide relay is the major import machinery for soluble proteins in the IMS. Its major component, the oxidoreductase MIA40, interacts with incoming substrates, retains them in the IMS, and oxidatively folds them. After this reaction, MIA40 is reoxidized by the sulfhydryl oxidase augmenter of liver regeneration, which couples disulfide formation by this machinery to the activity of the respiratory chain. In this review, we will discuss the import of IMS proteins with a focus on recent findings showing the diversity of disulfide relay substrates, describing the cytosolic control of this import system and highlighting the physiological relevance of the disulfide relay machinery in higher eukaryotes.

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