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

Autor:	Salscheider SL; Institute for Biochemistry, University of Cologne, Cologne, Germany., Gerlich S; Institute for Biochemistry, University of Cologne, Cologne, Germany., Cabrera-Orefice A; Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands., Peker E; Institute for Biochemistry, University of Cologne, Cologne, Germany., Rothemann RA; Institute for Biochemistry, University of Cologne, Cologne, Germany., Murschall LM; Institute for Biochemistry, University of Cologne, Cologne, Germany., Finger Y; Institute for Biochemistry, University of Cologne, Cologne, Germany., Szczepanowska K; Medical Faculty, Institute for Mitochondrial Diseases and Aging, University of Cologne, Cologne, Germany.; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany., Ahmadi ZA; Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands., Guerrero-Castillo S; Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands., Erdogan A; Institute for Biochemistry, University of Cologne, Cologne, Germany., Becker M; Institute for Biochemistry, University of Cologne, Cologne, Germany., Ali M; Institute for Biochemistry, University of Cologne, Cologne, Germany., Habich M; Institute for Biochemistry, University of Cologne, Cologne, Germany., Petrungaro C; Institute for Biochemistry, University of Cologne, Cologne, Germany., Burdina N; Institute for Biochemistry, University of Cologne, Cologne, Germany., Schwarz G; Institute for Biochemistry, University of Cologne, Cologne, Germany.; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.; Center for Molecular Medicine, University of Cologne, Cologne, Germany., Klußmann M; Institute for Biochemistry, University of Cologne, Cologne, Germany., Neundorf I; Institute for Biochemistry, University of Cologne, Cologne, Germany., Stroud DA; Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Vic., Australia., Ryan MT; Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Vic., Australia., Trifunovic A; Medical Faculty, Institute for Mitochondrial Diseases and Aging, University of Cologne, Cologne, Germany.; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.; Center for Molecular Medicine, University of Cologne, Cologne, Germany., Brandt U; Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany., Riemer J; Institute for Biochemistry, University of Cologne, Cologne, Germany.; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
Jazyk:	angličtina
Zdroj:	The EMBO journal [EMBO J] 2022 Sep 01; Vol. 41 (17), pp. e110784. Date of Electronic Publication: 2022 Jul 20.
DOI:	10.15252/embj.2022110784
Abstrakt:	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. (© 2022 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)
Databáze:	MEDLINE
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