A Role for p107 in Muscle Satellite Cell Self-Renewal

It is well established that skeletal muscle homeostasis is dependent on the activity of the muscle resident stem cells termed satellite cells (SCs). Many neuromuscular dystrophies and complications brought on from ageing are associated with decline to the SC population. Thus, there is a critical need to investigate the control mechanisms that dictate SC fate decisions for self-renewal that are crucial to maintain the SC population. A fundamental regulator of SC fate decisions is mitochondrial metabolism and thereby mitochondrial ATP generation via oxidative phosphorylation (OXPHOS). In our study we uncover a potential novel role for the transcriptional co-repressor retinoblastoma susceptibility protein like 1(Rbl1 or p107) in manipulating the self-renewal capacity of SCs through its mitochondrial localization under the control of the NAD+/NADH ratio. An investigation of this role for p107 function establishes a new mechanism to target SC decline and improve muscle regeneration that is required in muscular dystrophies and ageing.