Insulin-Degrading Enzyme Interacts with Mitochondrial Ribosomes and Respiratory Chain Proteins
Insulin-degrading enzyme (IDE) is a highly conserved metalloprotease that is mainly localized in the cytosol. Although IDE can degrade insulin and some other low molecular weight substrates efficiently, its ubiquitous expression suggests additional functions supported by experimental findings, such...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-05-01
|
| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/13/6/890 |
| _version_ | 1827738360236474368 |
|---|---|
| author | Ayse Yilmaz Chiara Guerrera Emmanuelle Waeckel-Énée Joanna Lipecka Barbara Bertocci Peter van Endert |
| author_facet | Ayse Yilmaz Chiara Guerrera Emmanuelle Waeckel-Énée Joanna Lipecka Barbara Bertocci Peter van Endert |
| author_sort | Ayse Yilmaz |
| collection | DOAJ |
| description | Insulin-degrading enzyme (IDE) is a highly conserved metalloprotease that is mainly localized in the cytosol. Although IDE can degrade insulin and some other low molecular weight substrates efficiently, its ubiquitous expression suggests additional functions supported by experimental findings, such as a role in stress responses and cellular protein homeostasis. The translation of a long full-length IDE transcript has been reported to result in targeting to mitochondria, but the role of IDE in this compartment is unknown. To obtain initial leads on the function of IDE in mitochondria, we used a proximity biotinylation approach to identify proteins interacting with wild-type and protease-dead IDE targeted to the mitochondrial matrix. We find that IDE interacts with multiple mitochondrial ribosomal proteins as well as with proteins involved in the synthesis and assembly of mitochondrial complex I and IV. The mitochondrial interactomes of wild type and mutant IDE are highly similar and do not reveal any likely proteolytic IDE substrates. We speculate that IDE could adopt similar additional non-proteolytic functions in mitochondria as in the cytosol, acting as a chaperone and contributing to protein homeostasis and stress responses. |
| first_indexed | 2024-03-11T02:43:17Z |
| format | Article |
| id | doaj.art-efcd5ab347e24b2098cf151936445e13 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-11T02:43:17Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-efcd5ab347e24b2098cf151936445e132023-11-18T09:30:16ZengMDPI AGBiomolecules2218-273X2023-05-0113689010.3390/biom13060890Insulin-Degrading Enzyme Interacts with Mitochondrial Ribosomes and Respiratory Chain ProteinsAyse Yilmaz0Chiara Guerrera1Emmanuelle Waeckel-Énée2Joanna Lipecka3Barbara Bertocci4Peter van Endert5Institut Necker Enfants Malades, Université Paris Cité, INSERM, CNRS, F-75015 Paris, FranceStructure Fédérative de Recherche Necker, Proteomics Platform, Université Paris Cité, INSERM, CNRS, F-75015 Paris, FranceInstitut Necker Enfants Malades, Université Paris Cité, INSERM, CNRS, F-75015 Paris, FranceStructure Fédérative de Recherche Necker, Proteomics Platform, Université Paris Cité, INSERM, CNRS, F-75015 Paris, FranceInstitut Necker Enfants Malades, Université Paris Cité, INSERM, CNRS, F-75015 Paris, FranceInstitut Necker Enfants Malades, Université Paris Cité, INSERM, CNRS, F-75015 Paris, FranceInsulin-degrading enzyme (IDE) is a highly conserved metalloprotease that is mainly localized in the cytosol. Although IDE can degrade insulin and some other low molecular weight substrates efficiently, its ubiquitous expression suggests additional functions supported by experimental findings, such as a role in stress responses and cellular protein homeostasis. The translation of a long full-length IDE transcript has been reported to result in targeting to mitochondria, but the role of IDE in this compartment is unknown. To obtain initial leads on the function of IDE in mitochondria, we used a proximity biotinylation approach to identify proteins interacting with wild-type and protease-dead IDE targeted to the mitochondrial matrix. We find that IDE interacts with multiple mitochondrial ribosomal proteins as well as with proteins involved in the synthesis and assembly of mitochondrial complex I and IV. The mitochondrial interactomes of wild type and mutant IDE are highly similar and do not reveal any likely proteolytic IDE substrates. We speculate that IDE could adopt similar additional non-proteolytic functions in mitochondria as in the cytosol, acting as a chaperone and contributing to protein homeostasis and stress responses.https://www.mdpi.com/2218-273X/13/6/890mitochondrionrespiratory chainmitochondrial translationchaperone |
| spellingShingle | Ayse Yilmaz Chiara Guerrera Emmanuelle Waeckel-Énée Joanna Lipecka Barbara Bertocci Peter van Endert Insulin-Degrading Enzyme Interacts with Mitochondrial Ribosomes and Respiratory Chain Proteins Biomolecules mitochondrion respiratory chain mitochondrial translation chaperone |
| title | Insulin-Degrading Enzyme Interacts with Mitochondrial Ribosomes and Respiratory Chain Proteins |
| title_full | Insulin-Degrading Enzyme Interacts with Mitochondrial Ribosomes and Respiratory Chain Proteins |
| title_fullStr | Insulin-Degrading Enzyme Interacts with Mitochondrial Ribosomes and Respiratory Chain Proteins |
| title_full_unstemmed | Insulin-Degrading Enzyme Interacts with Mitochondrial Ribosomes and Respiratory Chain Proteins |
| title_short | Insulin-Degrading Enzyme Interacts with Mitochondrial Ribosomes and Respiratory Chain Proteins |
| title_sort | insulin degrading enzyme interacts with mitochondrial ribosomes and respiratory chain proteins |
| topic | mitochondrion respiratory chain mitochondrial translation chaperone |
| url | https://www.mdpi.com/2218-273X/13/6/890 |
| work_keys_str_mv | AT ayseyilmaz insulindegradingenzymeinteractswithmitochondrialribosomesandrespiratorychainproteins AT chiaraguerrera insulindegradingenzymeinteractswithmitochondrialribosomesandrespiratorychainproteins AT emmanuellewaeckelenee insulindegradingenzymeinteractswithmitochondrialribosomesandrespiratorychainproteins AT joannalipecka insulindegradingenzymeinteractswithmitochondrialribosomesandrespiratorychainproteins AT barbarabertocci insulindegradingenzymeinteractswithmitochondrialribosomesandrespiratorychainproteins AT petervanendert insulindegradingenzymeinteractswithmitochondrialribosomesandrespiratorychainproteins |