Rôles et importance de la dynamique mitochondriale et de la mitophagie dans la physiologie musculaire et le développement de la sarcopénie

 

Gilles Gouspillou

Université du Québec à Montréal [UQAM]

 

Domaine : Appareil locomoteur et arthrite

Programme chercheurs-boursiers - Junior 1

Concours 2017-2018

Mitochondria are fascinating organelles regulating many critical cellular processes for skeletal muscle physiology. Indeed, they play central roles in muscle cell metabolism, energy supply, regulation of energy-sensitive signalling pathways, reactive oxygen species production/signalling, calcium homeostasis and the regulation of apoptosis. Given these multifaceted roles of mitochondria in fundamental aspects of muscle cell physiology, it is therefore not surprising that mitochondrial dysfunction has been implicated in a large number of adverse events/conditions affecting muscle health. This includes for instance the aging-related loss of muscle mass and function, disuse-induced muscle atrophy, muscular dystrophies, the development of insulin resistance, etc.

While the importance of normal mitochondrial function is well recognized for muscle physiology, there are important aspects of mitochondrial biology that are still poorly understood and investigated. These include mitochondrial dynamics (fusion and fission processes), morphology and processes involved in the removal of dysfunctional mitochondria such as mitophagy. Defining the mechanisms regulating these different aspects of mitochondrial biology, their importance for muscle physiology, as well as their interrelationships will be critical to further increase our understanding of the role played by mitochondria in skeletal muscle physiology and pathophysiology.

My research program precisely aims at pursuing these goals. To this end, my research program will (i) investigate the interrelations between mitochondrial function, morphology, dynamics and mitophagy in skeletal muscles, (ii) define the role of mitochondrial dynamics and mitophagy in skeletal muscle physiology and plasticity and (iii) uncover the mechanisms leading to, and the roles of, mitochondrial dysfunctions in the skeletal muscle aging-process. Overall, the present research program will generate tremendous and critical advancements in our understanding of the regulation of mitochondrial biology in skeletal cells and will shed new light on the role that mitochondria play in skeletal muscle function, plasticity and aging.