Grant: Project Grant

Muscle stem cells (MuSCs) located at the surface of mature skeletal muscle fibers play an essential role in sustaining muscle growth and repair in response to physiological and pathological conditions. As such, abnormalities in MuSC function underlie the decline in muscle regenerative capacity with age, and exacerbate muscle wasting in several forms of muscle dystrophies. One of the current challenges is thus to understand the molecular mechanisms of how MuSCs maintain their stem cell qualities in order to identify novel therapies to maintain muscle regenerative capacity which could also be employed as strategies to promote expansion and scale-up for stem cell-based therapies. With new avenues of research in stem cell biology, mitochondria, the cellular powerhouses, have emerged as central players in the maintenance of stem cell traits, and their decision to differentiate into mature repair tissue, thereby opening new opportunities to improve stem cell functions through modulation of their mitochondria. In this grant, we propose to explore the role of mitophagy as a regulator of mitochondrial properties in MuSCs and test whether this key mitochondrial quality control mechanism can be exploited therapeutically. Three aims are proposed: 1)Define the role of various mitophagy pathways on MuSC function 2)Delineate the mechanisms linking mitophagy pathways to the regulation of MuSC function 3)Determine how mitophagy pathways contribute to MuSC dysfunction during aging and test the benefits of mitophagy enhancing strategies