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Updated: Jan 30, 2026

A Facile and Efficient Approach for the Production of Reversible Disulfide Cross-linked Micelles
Published on: December 23, 2016
Vectorial Import via a Metastable Disulfide-Linked Complex Allows for a Quality Control Step and Import by the
Markus Habich1, Silja Lucia Salscheider1, Lena Maria Murschall1
1Institute for Biochemistry, Department of Chemistry, University of Cologne, Zuelpicher Str. 47a/R. 3.49, 50674 Cologne, Germany.
Abstract:
Disulfide formation in the mitochondrial intermembrane space (IMS) is an essential process. It is catalyzed by the disulfide relay machinery, which couples substrate import and oxidation. The machinery relies on the oxidoreductase and chaperone CHCHD4-Mia40. Here, we report on the driving force for IMS import and on a redox quality control mechanism. We demonstrate that unfolded reduced proteins, upon translocation into the IMS, initiate formation of a metastable disulfide-linked complex with CHCHD4. If this interaction does not result in productive oxidation, then substrates are released to the cytosol and degraded by the proteasome. Based on these data, we propose a redox quality control step at the level of the disulfide-linked intermediate that relies on the vectorial nature of IMS import. Our findings also provide the mechanistic framework to explain failures in import of numerous human disease mutants in CHCHD4 substrates.
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