p38α kinase governs muscle strength through PGC1α in mice

• Published in: Acta Physiologica Vol. 240; no. 11; pp. e14234 - n/a
• Main Authors: Herrera‐Melle, Leticia, Cicuéndez, Beatriz, López, Juan Antonio, Dumesic, Phillip A., Wilensky, Sarah E., Rodríguez, Elena, Leiva‐Vega, Luis, Caballero, Ainoa, León, Marta, Vázquez, Jesús, Spiegelman, Bruce M., Folgueira, Cintia, Mora, Alfonso, Sabio, Guadalupe
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.11.2024
• Subjects: Energy expenditure; Energy metabolism; Homeostasis; Locomotion; Metabolism; Mitochondria; mitochondrial biogenesis; mitochondrial dynamics; Muscle strength; Myoblasts; p38α; Proteomics; Quality of life; Skeletal muscle; muscle strength; skeletal muscle; mitochondrial biogenesis; mitochondrial dynamics; p38α
• ISSN: 1748-1708; 1748-1716; 1748-1716
• DOI: 10.1111/apha.14234

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. 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.