BCL6 regulates skeletal muscle mass and mitochondrial bioenergetics
Year: 2026
Type: article
Abstract: The transcriptional repressor B cell lymphoma 6 (BCL6) is highly expressed in skeletal muscle. Although transcriptome-wide studies have shown BCL6 dysregulation in muscular dystrophies, investigations into its endogenous roles in muscle biology remain scarce. We therefore generated skeletal muscle-specific Bcl6 knockout (M-Bcl6 KO) mice and used adeno-associated virus to knockdown (KD) Bcl6 selectively in limb muscles of mice. In both models, Bcl6 deficiency led to reduced muscle mass and contractility. Single-nucleus RNA sequencing and biochemical analyses revealed upregulation of Socs2, and inhibition of the IGF1/AKT pathway. Mitochondrial respiration was significantly reduced in permeabilized myofibers upon Bcl6 KO and KD, and electron microscopy showed decreased mitochondrial density and altered morphology. Pathways regulating mitochondrial quality control were also downregulated. While Bcl6 KO did not significantly impair baseline treadmill running capacity, it blunted the adaptive response to endurance training. These findings demonstrate that Bcl6 is a critical regulator of skeletal muscle mass and mitochondrial bioenergetics, acting through transcriptional control of signaling and metabolic pathways essential for the maintenance of muscle mass and function.
Source: Molecular Metabolism
Authors: Shirine E. Usmani, Jean-Philippe Leduc-Gaudet, Stephanie Chau, Catherine A. Bellissimo, Shabana Vohra, Krystel Desjardins, Evan Pollock-Tahiri, Irisa Shi, Felice Chun, Anthony Capobianco, Pascale Delisle, Wanda Dupebe, Marina Cefis, Vincent Marcangeli, Martha Ghebreselassie, Yu-Cheng Liang, Yasufumi Seki, Dominique Mayaki, Sabah Hussain, Ewan Goligher, Mohit Kapoor, Marius Locke, Gilles Gouspillou, Minna Woo
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,270
OpenAlex ID: W7154205898