Absence of MCJ/DnaJC15 promotes brown adipose tissue thermogenesis
Abstract Obesity poses a global health challenge, demanding a deeper understanding of adipose tissue (AT) and its mitochondria. This study describes the role of the mitochondrial protein Methylation-controlled J protein (MCJ/DnaJC15) in orchestrating brown adipose tissue (BAT) thermogenesis. Here we...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-01-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54353-4 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832594550490660864 |
|---|---|
| author | Beatriz Cicuéndez Alfonso Mora Juan Antonio López Andrea Curtabbi Javier Pérez-García Begoña Porteiro Daniel Jimenez-Blasco Pedro Latorre-Muro Paula Vo Madison Jerome Beatriz Gómez-Santos Rafael Romero-Becerra Magdalena Leiva Elena Rodríguez Marta León Luis Leiva-Vega Noemi Gómez-Lado Jorge L. Torres Lourdes Hernández-Cosido Pablo Aguiar Miguel Marcos Martin Jastroch Andreas Daiber Patricia Aspichueta Juan Pedro Bolaños Jessica B. Spinelli Pere Puigserver José Antonio Enriquez Jesús Vázquez Cintia Folgueira Guadalupe Sabio |
| author_facet | Beatriz Cicuéndez Alfonso Mora Juan Antonio López Andrea Curtabbi Javier Pérez-García Begoña Porteiro Daniel Jimenez-Blasco Pedro Latorre-Muro Paula Vo Madison Jerome Beatriz Gómez-Santos Rafael Romero-Becerra Magdalena Leiva Elena Rodríguez Marta León Luis Leiva-Vega Noemi Gómez-Lado Jorge L. Torres Lourdes Hernández-Cosido Pablo Aguiar Miguel Marcos Martin Jastroch Andreas Daiber Patricia Aspichueta Juan Pedro Bolaños Jessica B. Spinelli Pere Puigserver José Antonio Enriquez Jesús Vázquez Cintia Folgueira Guadalupe Sabio |
| author_sort | Beatriz Cicuéndez |
| collection | DOAJ |
| description | Abstract Obesity poses a global health challenge, demanding a deeper understanding of adipose tissue (AT) and its mitochondria. This study describes the role of the mitochondrial protein Methylation-controlled J protein (MCJ/DnaJC15) in orchestrating brown adipose tissue (BAT) thermogenesis. Here we show how MCJ expression decreases during obesity, as evident in human and mouse adipose tissue samples. MCJKO mice, even without UCP1, a fundamental thermogenic protein, exhibit elevated BAT thermogenesis. Electron microscopy unveils changes in mitochondrial morphology resembling BAT activation. Proteomic analysis confirms these findings and suggests involvement of the eIF2α mediated stress response. The pivotal role of eIF2α is scrutinized by in vivo CRISPR deletion of eIF2α in MCJKO mice, abrogating thermogenesis. These findings uncover the importance of MCJ as a regulator of BAT thermogenesis, presenting it as a promising target for obesity therapy. |
| format | Article |
| id | doaj-art-680f12e6ff5245c9830f5d0e0a4a7050 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-680f12e6ff5245c9830f5d0e0a4a70502025-01-19T12:32:03ZengNature PortfolioNature Communications2041-17232025-01-0116111610.1038/s41467-024-54353-4Absence of MCJ/DnaJC15 promotes brown adipose tissue thermogenesisBeatriz Cicuéndez0Alfonso Mora1Juan Antonio López2Andrea Curtabbi3Javier Pérez-García4Begoña Porteiro5Daniel Jimenez-Blasco6Pedro Latorre-Muro7Paula Vo8Madison Jerome9Beatriz Gómez-Santos10Rafael Romero-Becerra11Magdalena Leiva12Elena Rodríguez13Marta León14Luis Leiva-Vega15Noemi Gómez-Lado16Jorge L. Torres17Lourdes Hernández-Cosido18Pablo Aguiar19Miguel Marcos20Martin Jastroch21Andreas Daiber22Patricia Aspichueta23Juan Pedro Bolaños24Jessica B. Spinelli25Pere Puigserver26José Antonio Enriquez27Jesús Vázquez28Cintia Folgueira29Guadalupe Sabio30Centro Nacional de Investigaciones Cardiovasculares (CNIC)Centro Nacional de Investigaciones Cardiovasculares (CNIC)Centro Nacional de Investigaciones Cardiovasculares (CNIC)Centro Nacional de Investigaciones Cardiovasculares (CNIC)Organ Crosstalk in Metabolic Diseases Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO)Department of Physiology, CIMUS, University of Santiago de CompostelaCentro de Investigación Biomédica en Red sobre Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos IIIDepartment of Cancer Biology, Dana-Farber Cancer InstituteProgram in Molecular Medicine, UMass Chan Medical SchoolProgram in Molecular Medicine, UMass Chan Medical SchoolDepartment of Physiology, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU. Leioa, Biobizkaia Health Research InstituteCentro Nacional de Investigaciones Cardiovasculares (CNIC)Department of Immunology, School of Medicine, Universidad Complutense de MadridCentro Nacional de Investigaciones Cardiovasculares (CNIC)Centro Nacional de Investigaciones Cardiovasculares (CNIC)Centro Nacional de Investigaciones Cardiovasculares (CNIC)Molecular Imaging Biomarkers and Theragnosis Lab, Center for Research in Molecular Medicine and Chronic Diseases (CiMUS). University of Santiago de Compostela (USC)Complejo Asistencial de ZamoraBariatric Surgery Unit. Department of General Surgery, University Hospital of Salamanca. Department of Surgery. University of SalamancaMolecular Imaging Biomarkers and Theragnosis Lab, Center for Research in Molecular Medicine and Chronic Diseases (CiMUS). University of Santiago de Compostela (USC)Department of Internal Medicine, University Hospital of Salamanca-IBSALDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm UniversityDepartment of Cardiology 1, University Medical Center MainzDepartment of Physiology, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU. Leioa, Biobizkaia Health Research InstituteCentro de Investigación Biomédica en Red sobre Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos IIIProgram in Molecular Medicine, UMass Chan Medical SchoolDepartment of Cancer Biology, Dana-Farber Cancer InstituteCentro Nacional de Investigaciones Cardiovasculares (CNIC)Centro Nacional de Investigaciones Cardiovasculares (CNIC)Centro Nacional de Investigaciones Cardiovasculares (CNIC)Centro Nacional de Investigaciones Cardiovasculares (CNIC)Abstract Obesity poses a global health challenge, demanding a deeper understanding of adipose tissue (AT) and its mitochondria. This study describes the role of the mitochondrial protein Methylation-controlled J protein (MCJ/DnaJC15) in orchestrating brown adipose tissue (BAT) thermogenesis. Here we show how MCJ expression decreases during obesity, as evident in human and mouse adipose tissue samples. MCJKO mice, even without UCP1, a fundamental thermogenic protein, exhibit elevated BAT thermogenesis. Electron microscopy unveils changes in mitochondrial morphology resembling BAT activation. Proteomic analysis confirms these findings and suggests involvement of the eIF2α mediated stress response. The pivotal role of eIF2α is scrutinized by in vivo CRISPR deletion of eIF2α in MCJKO mice, abrogating thermogenesis. These findings uncover the importance of MCJ as a regulator of BAT thermogenesis, presenting it as a promising target for obesity therapy.https://doi.org/10.1038/s41467-024-54353-4 |
| spellingShingle | Beatriz Cicuéndez Alfonso Mora Juan Antonio López Andrea Curtabbi Javier Pérez-García Begoña Porteiro Daniel Jimenez-Blasco Pedro Latorre-Muro Paula Vo Madison Jerome Beatriz Gómez-Santos Rafael Romero-Becerra Magdalena Leiva Elena Rodríguez Marta León Luis Leiva-Vega Noemi Gómez-Lado Jorge L. Torres Lourdes Hernández-Cosido Pablo Aguiar Miguel Marcos Martin Jastroch Andreas Daiber Patricia Aspichueta Juan Pedro Bolaños Jessica B. Spinelli Pere Puigserver José Antonio Enriquez Jesús Vázquez Cintia Folgueira Guadalupe Sabio Absence of MCJ/DnaJC15 promotes brown adipose tissue thermogenesis Nature Communications |
| title | Absence of MCJ/DnaJC15 promotes brown adipose tissue thermogenesis |
| title_full | Absence of MCJ/DnaJC15 promotes brown adipose tissue thermogenesis |
| title_fullStr | Absence of MCJ/DnaJC15 promotes brown adipose tissue thermogenesis |
| title_full_unstemmed | Absence of MCJ/DnaJC15 promotes brown adipose tissue thermogenesis |
| title_short | Absence of MCJ/DnaJC15 promotes brown adipose tissue thermogenesis |
| title_sort | absence of mcj dnajc15 promotes brown adipose tissue thermogenesis |
| url | https://doi.org/10.1038/s41467-024-54353-4 |
| work_keys_str_mv | AT beatrizcicuendez absenceofmcjdnajc15promotesbrownadiposetissuethermogenesis AT alfonsomora absenceofmcjdnajc15promotesbrownadiposetissuethermogenesis AT juanantoniolopez absenceofmcjdnajc15promotesbrownadiposetissuethermogenesis AT andreacurtabbi absenceofmcjdnajc15promotesbrownadiposetissuethermogenesis AT javierperezgarcia absenceofmcjdnajc15promotesbrownadiposetissuethermogenesis AT begonaporteiro absenceofmcjdnajc15promotesbrownadiposetissuethermogenesis AT danieljimenezblasco absenceofmcjdnajc15promotesbrownadiposetissuethermogenesis AT pedrolatorremuro absenceofmcjdnajc15promotesbrownadiposetissuethermogenesis AT paulavo absenceofmcjdnajc15promotesbrownadiposetissuethermogenesis AT madisonjerome absenceofmcjdnajc15promotesbrownadiposetissuethermogenesis AT beatrizgomezsantos absenceofmcjdnajc15promotesbrownadiposetissuethermogenesis AT rafaelromerobecerra absenceofmcjdnajc15promotesbrownadiposetissuethermogenesis AT magdalenaleiva absenceofmcjdnajc15promotesbrownadiposetissuethermogenesis AT elenarodriguez absenceofmcjdnajc15promotesbrownadiposetissuethermogenesis AT martaleon absenceofmcjdnajc15promotesbrownadiposetissuethermogenesis AT luisleivavega absenceofmcjdnajc15promotesbrownadiposetissuethermogenesis AT noemigomezlado absenceofmcjdnajc15promotesbrownadiposetissuethermogenesis AT jorgeltorres absenceofmcjdnajc15promotesbrownadiposetissuethermogenesis AT lourdeshernandezcosido absenceofmcjdnajc15promotesbrownadiposetissuethermogenesis AT pabloaguiar absenceofmcjdnajc15promotesbrownadiposetissuethermogenesis AT miguelmarcos absenceofmcjdnajc15promotesbrownadiposetissuethermogenesis AT martinjastroch absenceofmcjdnajc15promotesbrownadiposetissuethermogenesis AT andreasdaiber absenceofmcjdnajc15promotesbrownadiposetissuethermogenesis AT patriciaaspichueta absenceofmcjdnajc15promotesbrownadiposetissuethermogenesis AT juanpedrobolanos absenceofmcjdnajc15promotesbrownadiposetissuethermogenesis AT jessicabspinelli absenceofmcjdnajc15promotesbrownadiposetissuethermogenesis AT perepuigserver absenceofmcjdnajc15promotesbrownadiposetissuethermogenesis AT joseantonioenriquez absenceofmcjdnajc15promotesbrownadiposetissuethermogenesis AT jesusvazquez absenceofmcjdnajc15promotesbrownadiposetissuethermogenesis AT cintiafolgueira absenceofmcjdnajc15promotesbrownadiposetissuethermogenesis AT guadalupesabio absenceofmcjdnajc15promotesbrownadiposetissuethermogenesis |