Tag: mitochondria (Page 1 of 5)

Metabolism and Cancer meeting (20-22 May 2026)

09/04/2026 / Sabio lab

Registration for the CNIO CaixaResearch Frontiers Meeting Metabolism and Cancer: Insights from Obesity and Beyond is open until 5 May 2026.

Application form

Held at CNIO Auditoriom from 20 to 22 may 2026, the meeting will highlight key drivers stemming from unhealthy metabolism that impact cancer development. It will delve into cutting-edge topics such as advancements in adipocyte biology, uncovering the diverse roles of adipose tissue beyond fat storage and its influence on tumor metabolism. Additionally, groundbreaking research on exercise and its potential impact on cancer will be presented. The role of mitochondrial bioenergetics in metabolic regulation will be rigorously examined, offering promising avenues for cancer therapy.

Moreover, the conference will scrutinize the tumor microenvironment and metabolic changes in surrounding tissues, alongside immune modulation,
particularly in the context of obesity. Cachexia, a complex syndrome involving muscle wasting and its relationship with cancer, will also be a focal point.

Preliminary Programme

Absence of MCJ/DnaJC15 promotes brown adipose tissue thermogenesis

13/01/2025 / Sabio lab

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. MCJ^KO 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 MCJ^KO 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.

Nat Commun (2025); 16: 229.

p38α kinase governs muscle strength through PGC1α in mice

07/10/2024 / Sabio lab

Leticia Herrera-Melle, Beatriz Cicuéndez, Juan Antonio López, Phillip A. Dumesic, Sarah E. Wilensky, Elena Rodríguez, Luis Leiva-Vega, Ainoa Caballero, Marta 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, p38α^MCK-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.

Acta Physiol (Oxf) 2024; 3:e14234.