AIFM1 is a component of the mitochondrial disulfide relay that drives complex I assembly through efficient import of NDUFS5

SL Salscheider; S Gerlich; A Cabrera-Orefice; E Peker; RA Rothemann; LM Murschall; Y Finger; K Szczepanowska; ZA Ahmadi; S Guerrero-Castillo; A Erdogan; M Becker; M Ali; M Habich; C Petrungaro; N Burdina; G Schwarz; M Klußmann; I Neundorf; DA Stroud; MT Ryan; A Trifunovic; U Brandt; J Riemer

Journal article

AIFM1 is a component of the mitochondrial disulfide relay that drives complex I assembly through efficient import of NDUFS5

SL Salscheider, S Gerlich, A Cabrera-Orefice, E Peker, RA Rothemann, LM Murschall, Y Finger, K Szczepanowska, ZA Ahmadi, S Guerrero-Castillo, A Erdogan, M Becker, M Ali, M Habich, C Petrungaro, N Burdina, G Schwarz, M Klußmann, I Neundorf, DA Stroud Show all

EMBO Journal | SPRINGERNATURE | Published : 2022

DOI: 10.15252/embj.2022110784

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Abstract

The mitochondrial intermembrane space protein AIFM1 has been reported to mediate the import of MIA40/CHCHD4, which forms the import receptor in the mitochondrial disulfide relay. Here, we demonstrate that AIFM1 and MIA40/CHCHD4 cooperate beyond this MIA40/CHCHD4 import. We show that AIFM1 and MIA40/CHCHD4 form a stable long-lived complex in vitro, in different cell lines, and in tissues. In HEK293 cells lacking AIFM1, levels of MIA40 are unchanged, but the protein is present in the monomeric form. Monomeric MIA40 neither efficiently interacts with nor mediates the import of specific substrates. The import defect is especially severe for NDUFS5, a subunit of complex I of the respiratory chain..

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University of Melbourne Researchers

David Stroud Author

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Grants

Awarded by National Health and Medical Research Council

Funding Acknowledgements

The Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) funds research in the Laboratory of JR through the grants RI2150/5-1, RI2150/2-2, RTG2550/1, and CRC1218-Project number 269925409. Research in the lab of UB is funded by CRC1218-Project number 269925409 and grants from the Netherlands Organization for Health Research and Development (TOP 91217009) and the Netherlands Organization for Scientific Research (TOP 714.017.00 4). Research in the lab of AT is funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) including CRC1218-Project number 269925409. We thank the Monash Biomedical Proteomics Facility and Monash Flowcore for the provision of instrumentation, training, and technical support. We acknowledge funding from the National Health and Medical Research Council (NHMRC Project Grants 1164459 to MTR; 1125390, 1140906 to MTR and DAS; NHMRC Fellowship 1140851 to DAS). We thank the CECAD Proteome and Imaging Facilities for the provision of instrumentation, training, and technical support. Open Access funding enabled and organized by Projekt DEAL.