Bottinelli

Skeletal muscle structural and functional heterogeneity and plasticity in health and disease

Skeletal muscles are the tools for animals and human beings to interact with their environment. All movements result from skeletal muscle contraction: locomotion, eating, biting, but also speaking or writing are made possible only by skeletal muscle contraction. Moreover, skeletal muscle, representing 40% of body weight and being a major site of insulin action, plays a major role in body metabolism.  A growing body of information suggests, in fact, that muscle atrophy induced by disuse contributes to whole body impairment in energy metabolism and is a major cause of metabolic diseases.

Skeletal muscles shows a high structural and functional heterogeneity and a high degree of plasticity, namely their structure and function can deeply adapt to physiologic and pathologic conditions such as exercise training, disuse, ageing, muscular dystrophy, chronic non muscle diseases, drug administration. Skeletal muscle plasticity is of paramount importance to enable the body to improve or simply maintain physical performance, and to cope with changes in energy and amino acid supply such as those occurring in starvation or chronic diseases. Our research group has been working since the 80s on the cellular and molecular mechanisms underlying the latter phenomena.

To achieve our goal we combine the analysis of muscle structure and function in both humans and small mammals. The functional analysis of force and shortening velocity are performed at all levels of organization: whole body; isolated muscles in vitro; individual muscle fibres; isolated myosin, the muscle molecular motor, working in reconstituted contractile systems in vitro. The samples used for functional analysis can be subjected to the following structural analyses: (i) muscle fibers size and type by immuno-histochemistry; (ii) concentration of myosin and myofibrillar proteins by quantitative electrophoresis; (iii) expression of myofibrillar proteins isoforms by high resolutions SDS-PAGE and Western blot; (iv) global protein pattern and post-translational modifications of proteins by proteomics; (v) intracellular signaling pathways controlling muscle mass and metabolism.

We have given a relevant contribution to: (i) the understanding of the role of myosin isoforms in determining the contractile and energetic properties of skeletal muscle fibres; (ii) the identification of the molecular mechanisms underlying myosin isoform functional diversity; (iii) the understanding of the mechanisms underlying the functional adaptation to exercise, ageing, disuse and muscular dystrophy.