Nature Communications (Jan 2025)
Absence of MCJ/DnaJC15 promotes brown adipose tissue thermogenesis
- 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
Affiliations
- Beatriz Cicuéndez
- Centro Nacional de Investigaciones Cardiovasculares (CNIC)
- Alfonso Mora
- Centro Nacional de Investigaciones Cardiovasculares (CNIC)
- Juan Antonio López
- Centro Nacional de Investigaciones Cardiovasculares (CNIC)
- Andrea Curtabbi
- Centro Nacional de Investigaciones Cardiovasculares (CNIC)
- Javier Pérez-García
- Organ Crosstalk in Metabolic Diseases Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO)
- Begoña Porteiro
- Department of Physiology, CIMUS, University of Santiago de Compostela
- Daniel Jimenez-Blasco
- Centro de Investigación Biomédica en Red sobre Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III
- Pedro Latorre-Muro
- Department of Cancer Biology, Dana-Farber Cancer Institute
- Paula Vo
- Program in Molecular Medicine, UMass Chan Medical School
- Madison Jerome
- Program in Molecular Medicine, UMass Chan Medical School
- Beatriz Gómez-Santos
- Department of Physiology, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU. Leioa, Biobizkaia Health Research Institute
- Rafael Romero-Becerra
- Centro Nacional de Investigaciones Cardiovasculares (CNIC)
- Magdalena Leiva
- Department of Immunology, School of Medicine, Universidad Complutense de Madrid
- Elena Rodríguez
- Centro Nacional de Investigaciones Cardiovasculares (CNIC)
- Marta León
- Centro Nacional de Investigaciones Cardiovasculares (CNIC)
- Luis Leiva-Vega
- Centro Nacional de Investigaciones Cardiovasculares (CNIC)
- Noemi Gómez-Lado
- Molecular Imaging Biomarkers and Theragnosis Lab, Center for Research in Molecular Medicine and Chronic Diseases (CiMUS). University of Santiago de Compostela (USC)
- Jorge L. Torres
- Complejo Asistencial de Zamora
- Lourdes Hernández-Cosido
- Bariatric Surgery Unit. Department of General Surgery, University Hospital of Salamanca. Department of Surgery. University of Salamanca
- Pablo Aguiar
- Molecular Imaging Biomarkers and Theragnosis Lab, Center for Research in Molecular Medicine and Chronic Diseases (CiMUS). University of Santiago de Compostela (USC)
- Miguel Marcos
- Department of Internal Medicine, University Hospital of Salamanca-IBSAL
- Martin Jastroch
- Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University
- Andreas Daiber
- Department of Cardiology 1, University Medical Center Mainz
- Patricia Aspichueta
- Department of Physiology, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU. Leioa, Biobizkaia Health Research Institute
- Juan Pedro Bolaños
- Centro de Investigación Biomédica en Red sobre Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III
- Jessica B. Spinelli
- Program in Molecular Medicine, UMass Chan Medical School
- Pere Puigserver
- Department of Cancer Biology, Dana-Farber Cancer Institute
- José Antonio Enriquez
- Centro Nacional de Investigaciones Cardiovasculares (CNIC)
- Jesús Vázquez
- Centro Nacional de Investigaciones Cardiovasculares (CNIC)
- Cintia Folgueira
- Centro Nacional de Investigaciones Cardiovasculares (CNIC)
- Guadalupe Sabio
- Centro Nacional de Investigaciones Cardiovasculares (CNIC)
- DOI
- https://doi.org/10.1038/s41467-024-54353-4
- Journal volume & issue
-
Vol. 16,
no. 1
pp. 1 – 16
Abstract
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.
