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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/...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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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. |
format | Online Article Text |
id | pubmed-9434101 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
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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