The mitochondrial oxidoreductase CHCHD4 is present in a semi-oxidized state in vivo
Alican J. Erdogan,
Muna Ali,
Markus Habich,
Silja L. Salscheider,
Laura Schu,
Carmelina Petrungaro,
Luke W. Thomas,
Margaret Ashcroft,
Lars I. Leichert,
Leticia Prates Roma,
Jan Riemer
Affiliations
Alican J. Erdogan
Department of Chemistry, Institute of Biochemistry, University of Cologne, Zuelpicher Str. 47a, 50674 Cologne, Germany
Muna Ali
Department of Chemistry, Institute of Biochemistry, University of Cologne, Zuelpicher Str. 47a, 50674 Cologne, Germany; Department of Biology, Cellular Biochemistry, University of Kaiserslautern, Erwin-Schroedinger-Str. 13, 67663 Kaiserslautern, Germany
Markus Habich
Department of Chemistry, Institute of Biochemistry, University of Cologne, Zuelpicher Str. 47a, 50674 Cologne, Germany
Silja L. Salscheider
Department of Chemistry, Institute of Biochemistry, University of Cologne, Zuelpicher Str. 47a, 50674 Cologne, Germany
Laura Schu
Department of Biology, Cellular Biochemistry, University of Kaiserslautern, Erwin-Schroedinger-Str. 13, 67663 Kaiserslautern, Germany
Carmelina Petrungaro
Department of Chemistry, Institute of Biochemistry, University of Cologne, Zuelpicher Str. 47a, 50674 Cologne, Germany
Luke W. Thomas
Department of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK
Margaret Ashcroft
Department of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK
Lars I. Leichert
Institute for Biochemistry and Pathobiochemistry - Microbial Biochemistry, Ruhr-Universität Bochum, 44797 Bochum, Germany
Leticia Prates Roma
Biophysics Department, Center for Integrative Physiology and Molecular Medicine, Saarland University, 66421 Homburg, Saar, Germany
Jan Riemer
Department of Chemistry, Institute of Biochemistry, University of Cologne, Zuelpicher Str. 47a, 50674 Cologne, Germany; Corresponding author.
Disulfide formation in the mitochondrial intermembrane space is an essential process catalyzed by a disulfide relay machinery. In mammalian cells, the key enzyme in this machinery is the oxidoreductase CHCHD4/Mia40. Here, we determined the in vivo CHCHD4 redox state, which is the major determinant of its cellular activity. We found that under basal conditions, endogenous CHCHD4 redox state in cultured cells and mouse tissues was predominantly oxidized, however, degrees of oxidation in different tissues varied from 70% to 90% oxidized. To test whether differences in the ratio between CHCHD4 and ALR might explain tissue-specific differences in the CHCHD4 redox state, we determined the molar ratio of both proteins in different mouse tissues. Surprisingly, ALR is superstoichiometric over CHCHD4 in most tissues. However, the levels of CHCHD4 and the ratio of ALR over CHCHD4 appear to correlate only weakly with the redox state, and although ALR is present in superstoichiometric amounts, it does not lead to fully oxidized CHCHD4. Keywords: CHCHD4/ALR/disulfide/redox/mitochondria
