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BCL6 regulates skeletal muscle mass and mitochondrial bioenergetics

ABSTRACT: The transcriptional repressor B cell lymphoma 6 (BCL6) is highly expressed in skeletal muscles. 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 viruses to knockdown (KD) Bcl6. In both models, BCL6 deficiency led to reduced muscle mass and contractility. Single-nucleus RNA sequencing, ATAC-seq, and biochemical analyses revealed upregulation of Socs2, 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. 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE306646 | GEO | 2026/05/15

REPOSITORIES: GEO

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