at the CNIO

Tag: mitochondria (Page 1 of 5)

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.

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.

Mitochondia from brown fat (Image: Beatriz Cicuéndez).

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.

p38α kinase governs muscle strength through PGC1α in mice

Leticia Herrera-Melle, Beatriz Cicuéndez, Juan Antonio López, Phillip A. Dumesic, Sarah E. Wilensky, Elena RodríguezLuis Leiva-VegaAinoa CaballeroMarta León, Jesús Vázquez, Bruce M. Spiegelman, Cintia Folgueira, Alfonso Mora & Guadalupe Sabio.

Aims: skeletal muscle, with its remarkable plasticity and dynamic adaptation, serves as a cornerstone of locomotion and metabolic homeostasis in the human body. Muscle tissue, with its extraordinary capacity for force generation and energy expenditure, plays a fundamental role in the movement, metabolism, and overall health. In this context, we sought to determine the role of p38α in mitochondrial metabolism since mitochondrial dynamics play a crucial role in the development of muscle-related diseases that result in muscle weakness.

Higher muscle strength in p38αMCK-KO mice (Image: Alfonso Mora).

Methods: we conducted our study using male mice (MCK-cre, p38αMCK-KO and PGC1α MCK-KO) and mouse primary myoblasts. We analyzed mitochondrial metabolic, physiological parameters as well as proteomics, western blot, RNA-seq analysis from muscle samples.

Results: our findings highlight the critical involvement of muscle p38α in the regulation of mitochondrial function, a key determinant of muscle strength. The absence of p38α triggers changes in mitochondrial dynamics through the activation of PGC1α, a central regulator of mitochondrial biogenesis. These results have substantial implications for understanding the complex interplay between p38α kinase, PGC1α activation, and mitochondrial content, thereby enhancing our knowledge in the control of muscle biology.

Conclusions: this knowledge holds relevance for conditions associated with muscle weakness, where disruptions in these molecular pathways are frequently implicated in diminishing physical strength. Our research underscores the potential importance of targeting the p38α and PGC1α pathways within muscle, offering promising avenues for the advancement of innovative treatments. Such interventions hold the potential to improve the quality of life for individuals affected by muscle-related diseases.

The IBSA Foundation awards Cintia Folgueira

The 11th edition of the IBSA Foundation fellowship program had a record number of projects received. A total of 248 applicants from over 50 countries.

Cintia Folgueira was awarded in Endocrinology with 32,000 € for her project Exploring new insights into brown adipose tissue mitochondria for protection against endocrine disorders. She will investigate valuable insights into prospective therapeutic targets for addressing obesity and related metabolic disorders, particularly by underscoring that the absence of mitochondrial proteins correlates with improvements in obesity, adiposity, and glucose tolerance.

The winner for the area “Endocrinology”, Cintia Folgueira Cobos.
« Older posts

© 2025 Sabio lab

Theme by Anders NorénUp ↑