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Absence of MCJ/DnaJC15 promotes brown adipose tissue thermogenesis

Author

Listed:
  • Beatriz Cicuéndez

    (Centro Nacional de Investigaciones Cardiovasculares (CNIC)
    Spanish National Cancer Centre (CNIO))

  • Alfonso Mora

    (Centro Nacional de Investigaciones Cardiovasculares (CNIC)
    Spanish National Cancer Centre (CNIO))

  • Juan Antonio López

    (Centro Nacional de Investigaciones Cardiovasculares (CNIC)
    Instituto de Salud Carlos III)

  • Andrea Curtabbi

    (Centro Nacional de Investigaciones Cardiovasculares (CNIC)
    Instituto de Salud Carlos III)

  • Javier Pérez-García

    (Spanish National Cancer Centre (CNIO))

  • Begoña Porteiro

    (University of Santiago de Compostela
    Instituto de Salud Carlos III)

  • Daniel Jimenez-Blasco

    (Instituto de Salud Carlos III
    CSIC
    CSIC)

  • Pedro Latorre-Muro

    (Dana-Farber Cancer Institute
    Harvard Medical School)

  • 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)
    Spanish National Cancer Centre (CNIO))

  • Marta León

    (Centro Nacional de Investigaciones Cardiovasculares (CNIC)
    Spanish National Cancer Centre (CNIO))

  • Luis Leiva-Vega

    (Centro Nacional de Investigaciones Cardiovasculares (CNIC)
    Spanish National Cancer Centre (CNIO))

  • Noemi Gómez-Lado

    (Center for Research in Molecular Medicine and Chronic Diseases (CiMUS). University of Santiago de Compostela (USC)
    Health Research Institute of Santiago de Compostela (IDIS)
    University Clinical Hospital of Santiago de Compostela (CHUS))

  • 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)
    Health Research Institute of Santiago de Compostela (IDIS)
    University Clinical Hospital of Santiago de Compostela (CHUS))

  • Miguel Marcos

    (University Hospital of Salamanca-IBSAL
    Department of Medicine. University of Salamanca)

  • Martin Jastroch

    (Stockholm University)

  • Andreas Daiber

    (University Medical Center Mainz
    Partner Site Rhine-Main)

  • Patricia Aspichueta

    (Biobizkaia Health Research Institute
    Instituto de Salud Carlos III)

  • Juan Pedro Bolaños

    (Instituto de Salud Carlos III
    CSIC
    CSIC)

  • Jessica B. Spinelli

    (UMass Chan Medical School
    UMass Chan Medical School Cancer Center)

  • Pere Puigserver

    (Dana-Farber Cancer Institute
    Harvard Medical School)

  • José Antonio Enriquez

    (Centro Nacional de Investigaciones Cardiovasculares (CNIC)
    Instituto de Salud Carlos III)

  • Jesús Vázquez

    (Centro Nacional de Investigaciones Cardiovasculares (CNIC)
    Instituto de Salud Carlos III)

  • Cintia Folgueira

    (Centro Nacional de Investigaciones Cardiovasculares (CNIC)
    Spanish National Cancer Centre (CNIO)
    Instituto de Salud Carlos III)

  • Guadalupe Sabio

    (Centro Nacional de Investigaciones Cardiovasculares (CNIC)
    Spanish National Cancer Centre (CNIO))

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.

Suggested Citation

  • 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, 2025. "Absence of MCJ/DnaJC15 promotes brown adipose tissue thermogenesis," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-024-54353-4
    DOI: 10.1038/s41467-024-54353-4
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