BCL6 regulates skeletal muscle mass and mitochondrial bioenergetics

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.