Salscheider, Silja Lucia, Gerlich, Sarah, Cabrera-Orefice, Alfredo ORCID: 0000-0002-2042-3794, Peker, Esra, Rothemann, Robin Alexander, Murschall, Lena Maria, Finger, Yannik, Szczepanowska, Karolina ORCID: 0000-0003-4689-2350, Ahmadi, Zeinab Alsadat, Guerrero-Castillo, Sergio ORCID: 0000-0002-6630-0562, Erdogan, Alican, Becker, Mark ORCID: 0000-0003-3474-2419, Ali, Muna, Habich, Markus, Petrungaro, Carmelina, Burdina, Nele, Schwarz, Guenter, Klussmann, Merlin, Neundorf, Ines, Stroud, David A., Ryan, Michael T., Trifunovic, Aleksandra ORCID: 0000-0002-5472-3517, Brandt, Ulrich ORCID: 0000-0003-1869-6811 and Riemer, Jan (2022). AIFM1 is a component of the mitochondrial disulfide relay that drives complex I assembly through efficient import of NDUFS5. Embo J., 41 (17). HOBOKEN: WILEY. ISSN 1460-2075

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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. As a consequence, NDUFS5 accumulates in the cytosol and undergoes rapid proteasomal degradation. Lack of mitochondrial NDUFS5 in turn results in stalling of complex I assembly. Collectively, we demonstrate that AIFM1 serves two overlapping functions: importing MIA40/CHCHD4 and constituting an integral part of the disulfide relay that ensures efficient interaction of MIA40/CHCHD4 with specific substrates.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Salscheider, Silja LuciaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gerlich, SarahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cabrera-Orefice, AlfredoUNSPECIFIEDorcid.org/0000-0002-2042-3794UNSPECIFIED
Peker, EsraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rothemann, Robin AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Murschall, Lena MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Finger, YannikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Szczepanowska, KarolinaUNSPECIFIEDorcid.org/0000-0003-4689-2350UNSPECIFIED
Ahmadi, Zeinab AlsadatUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Guerrero-Castillo, SergioUNSPECIFIEDorcid.org/0000-0002-6630-0562UNSPECIFIED
Erdogan, AlicanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Becker, MarkUNSPECIFIEDorcid.org/0000-0003-3474-2419UNSPECIFIED
Ali, MunaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Habich, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Petrungaro, CarmelinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Burdina, NeleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schwarz, GuenterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klussmann, MerlinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neundorf, InesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stroud, David A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ryan, Michael T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Trifunovic, AleksandraUNSPECIFIEDorcid.org/0000-0002-5472-3517UNSPECIFIED
Brandt, UlrichUNSPECIFIEDorcid.org/0000-0003-1869-6811UNSPECIFIED
Riemer, JanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-679403
DOI: 10.15252/embj.2022110784
Journal or Publication Title: Embo J.
Volume: 41
Number: 17
Date: 2022
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 1460-2075
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
INTERMEMBRANE SPACE; PROTEIN IMPORT; MIA40; OXIDOREDUCTASE; BIOGENESIS; PATHWAY; SYSTEM; CHCHD4Multiple languages
Biochemistry & Molecular Biology; Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/67940

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