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

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/...

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Autores principales: Salscheider, Silja Lucia, Gerlich, Sarah, Cabrera‐Orefice, Alfredo, Peker, Esra, Rothemann, Robin Alexander, Murschall, Lena Maria, Finger, Yannik, Szczepanowska, Karolina, Ahmadi, Zeinab Alsadat, Guerrero‐Castillo, Sergio, Erdogan, Alican, Becker, Mark, Ali, Muna, Habich, Markus, Petrungaro, Carmelina, Burdina, Nele, Schwarz, Guenter, Klußmann, Merlin, Neundorf, Ines, Stroud, David A, Ryan, Michael T, Trifunovic, Aleksandra, Brandt, Ulrich, Riemer, Jan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9434101/
https://www.ncbi.nlm.nih.gov/pubmed/35859387
http://dx.doi.org/10.15252/embj.2022110784
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author Salscheider, Silja Lucia
Gerlich, Sarah
Cabrera‐Orefice, Alfredo
Peker, Esra
Rothemann, Robin Alexander
Murschall, Lena Maria
Finger, Yannik
Szczepanowska, Karolina
Ahmadi, Zeinab Alsadat
Guerrero‐Castillo, Sergio
Erdogan, Alican
Becker, Mark
Ali, Muna
Habich, Markus
Petrungaro, Carmelina
Burdina, Nele
Schwarz, Guenter
Klußmann, Merlin
Neundorf, Ines
Stroud, David A
Ryan, Michael T
Trifunovic, Aleksandra
Brandt, Ulrich
Riemer, Jan
author_facet Salscheider, Silja Lucia
Gerlich, Sarah
Cabrera‐Orefice, Alfredo
Peker, Esra
Rothemann, Robin Alexander
Murschall, Lena Maria
Finger, Yannik
Szczepanowska, Karolina
Ahmadi, Zeinab Alsadat
Guerrero‐Castillo, Sergio
Erdogan, Alican
Becker, Mark
Ali, Muna
Habich, Markus
Petrungaro, Carmelina
Burdina, Nele
Schwarz, Guenter
Klußmann, Merlin
Neundorf, Ines
Stroud, David A
Ryan, Michael T
Trifunovic, Aleksandra
Brandt, Ulrich
Riemer, Jan
author_sort Salscheider, Silja Lucia
collection PubMed
description 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.
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spelling pubmed-94341012022-09-09 AIFM1 is a component of the mitochondrial disulfide relay that drives complex I assembly through efficient import of NDUFS5 Salscheider, Silja Lucia Gerlich, Sarah Cabrera‐Orefice, Alfredo Peker, Esra Rothemann, Robin Alexander Murschall, Lena Maria Finger, Yannik Szczepanowska, Karolina Ahmadi, Zeinab Alsadat Guerrero‐Castillo, Sergio Erdogan, Alican Becker, Mark Ali, Muna Habich, Markus Petrungaro, Carmelina Burdina, Nele Schwarz, Guenter Klußmann, Merlin Neundorf, Ines Stroud, David A Ryan, Michael T Trifunovic, Aleksandra Brandt, Ulrich Riemer, Jan EMBO J Articles 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. John Wiley and Sons Inc. 2022-07-20 /pmc/articles/PMC9434101/ /pubmed/35859387 http://dx.doi.org/10.15252/embj.2022110784 Text en © 2022 The Authors. Published under the terms of the CC BY NC ND 4.0 license. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Articles
Salscheider, Silja Lucia
Gerlich, Sarah
Cabrera‐Orefice, Alfredo
Peker, Esra
Rothemann, Robin Alexander
Murschall, Lena Maria
Finger, Yannik
Szczepanowska, Karolina
Ahmadi, Zeinab Alsadat
Guerrero‐Castillo, Sergio
Erdogan, Alican
Becker, Mark
Ali, Muna
Habich, Markus
Petrungaro, Carmelina
Burdina, Nele
Schwarz, Guenter
Klußmann, Merlin
Neundorf, Ines
Stroud, David A
Ryan, Michael T
Trifunovic, Aleksandra
Brandt, Ulrich
Riemer, Jan
AIFM1 is a component of the mitochondrial disulfide relay that drives complex I assembly through efficient import of NDUFS5
title AIFM1 is a component of the mitochondrial disulfide relay that drives complex I assembly through efficient import of NDUFS5
title_full AIFM1 is a component of the mitochondrial disulfide relay that drives complex I assembly through efficient import of NDUFS5
title_fullStr AIFM1 is a component of the mitochondrial disulfide relay that drives complex I assembly through efficient import of NDUFS5
title_full_unstemmed AIFM1 is a component of the mitochondrial disulfide relay that drives complex I assembly through efficient import of NDUFS5
title_short AIFM1 is a component of the mitochondrial disulfide relay that drives complex I assembly through efficient import of NDUFS5
title_sort aifm1 is a component of the mitochondrial disulfide relay that drives complex i assembly through efficient import of ndufs5
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9434101/
https://www.ncbi.nlm.nih.gov/pubmed/35859387
http://dx.doi.org/10.15252/embj.2022110784
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