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 () and Guadalupe Sabio ()
Additional contact information
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: Spanish National Cancer Centre (CNIO)
Begoña Porteiro: University of Santiago de Compostela
Daniel Jimenez-Blasco: Instituto de Salud Carlos III
Pedro Latorre-Muro: Dana-Farber Cancer Institute
Paula Vo: UMass Chan Medical School
Madison Jerome: UMass Chan Medical School
Beatriz Gómez-Santos: Biobizkaia Health Research Institute
Rafael Romero-Becerra: Centro Nacional de Investigaciones Cardiovasculares (CNIC)
Magdalena Leiva: 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: 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: University Hospital of Salamanca. Department of Surgery. University of Salamanca
Pablo Aguiar: Center for Research in Molecular Medicine and Chronic Diseases (CiMUS). University of Santiago de Compostela (USC)
Miguel Marcos: University Hospital of Salamanca-IBSAL
Martin Jastroch: Stockholm University
Andreas Daiber: University Medical Center Mainz
Patricia Aspichueta: Biobizkaia Health Research Institute
Juan Pedro Bolaños: Instituto de Salud Carlos III
Jessica B. Spinelli: UMass Chan Medical School
Pere Puigserver: 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)

Nature Communications, 2025, vol. 16, issue 1, 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.

Date: 2025
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-54353-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-024-54353-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-54353-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().