Enhanced Energetic State and Protection from Oxidative Stress in Human Myoblasts Overexpressing BMI1

Abstract

Summary: The Polycomb group gene BMI1 is essential for efficient muscle regeneration in a mouse model of Duchenne muscular dystrophy, and its enhanced expression in adult skeletal muscle satellite cells ameliorates the muscle strength in this model. Here, we show that the impact of mild BMI1 overexpression observed in mouse models is translatable to human cells. In human myoblasts, BMI1 overexpression increases mitochondrial activity, leading to an enhanced energetic state with increased ATP production and concomitant protection against DNA damage both in vitro and upon xenografting in a severe dystrophic mouse model. These preclinical data in mouse models and human cells provide a strong rationale for the development of pharmacological approaches to target BMI1-mediated mitochondrial regulation and protection from DNA damage to sustain the regenerative potential of the skeletal muscle in conditions of chronic muscle wasting. : In this article, Marino and colleagues show that BMI1 overexpression in human myoblasts enhanced their energetic state while conferring protection from DNA damage both in vitro and in vivo upon xenografting in a dystrophic mouse model. These preclinical data provide a strong rationale for the development of pharmacological approaches to target BMI1-mediated mitochondrial regulation and protection from DNA damage to sustain the regenerative potential of the skeletal muscle. Keywords: Polycomb gene, satellite cells, muscle regeneration, myopathy, DMD, myoblasts, oxidative phosphorylation