A non-canonical role for p107 in muscle stem cell fate decisions

The regenerative potential of skeletal muscle is attributed to the presence of resident muscle stem cells known as satellite cells (SCs). After activation SCs have two fates, either to differentiate into new muscle or self-renew to replenish their population. Dysregulation in favor of one outcome over the other has been implicated in loss of muscular regenerative capacity. Mitochondrial metabolism has recently emerged as a regulator of SC fate decisions. We uncovered a non-canonical mitochondrial role for retinoblastoma-like protein 1 (Rbl1, p107) in manipulating fate decisions through its effect on mitochondrial dynamics. We find that in the absence of mitochondrially localized p107, SCs display a higher rate of self-renewal, while also exhibiting higher mitochondrial connectivity. This was associated with increases in the mitochondrial fusion protein OPA1, as well as a loss in cellular acetylation. Taken together, these findings suggest that non-canonical p107 function in SCs controls their cell fate decisions.