Feliciano Protasi
University G. d’Annunzio of Chieti Pescara,
Italy
Abstract Title:
Improper Remodeling of Organelles Deputed to Ca2+ Handling and Aerobic ATP Production Underlies Muscle Dysfunction in Ageing.
Biography:
Feliciano Protasi is Professor of Physiology at the University G. d’Annunzio of Chieti-Pescara (Italy) and directs a multi-disciplinary research program mainly supported by Telethon ONLUS (Italy) and by the National Institute of Health (USA). After graduating in 1991 in Biological Sciences at the University of Perugia (Italy), Dr. Protasi moved to the USA to join first the laboratory of Prof. Clara Franzini-Armstrong (1993-1997) at the Univ. of Pennsylvania (Philadelphia, PA), and then the lab of Prof. Paul D. Allen at the Harvard Medical School (Boston, MA). Dr. Protasi returned to Italy in 2002 as Associate Professor to join the newly opened institute CeSI (Center for Research of Ageing at Ud’A). He soon established his own lines of research, mainly focused in unraveling the patho-physiological mechanisms underlying ageing and myopathies caused by alterations in Ca2+ handling in striated muscles
Research Interests:
Proper skeletal muscle function is controlled by intracellular Ca2+ concentration and by efficient production of energy (ATP), which in turn depend on: (a) release and re-uptake of Ca2+ from sarcoplasmic-reticulum during excitation-contraction (EC) coupling, which controls the contraction and relaxation of sarcomeres; (b) uptake of Ca2+ into the mitochondrial matrix, which stimulates aerobic ATP production; and finally (c) entry of Ca2+ from the extracellular space via store-operated Ca2+ entry (SOCE), a mechanism that is important to limit/delay muscle fatigue. Abnormalities in Ca2+ handling and inefficient ATP production underlie many physio-pathological conditions, including dysfunction in ageing. In different, but complementary, projects carried out in our laboratory in the past 15-20 years studying: i) structural and functional changes caused by ageing in muscle of humans and mice; and ii) the positive-rescuing effect of exercise, we collected compelling evidence that: a) sedentary ageing causes partial disarray/damage of membrane systems involved in EC coupling and SOCE (collectively the Sarcotubular System), and loss/misplacement of Mitochondria; b) regular exercise promote the rescue/maintenance of both Sarcotubular System and Mitochondria. All these structural changes were accompanied by related functional changes, i.e., loss/decay of function caused by sedentary ageing, and improved function associated to regular exercise. These findings demonstrate that the integrity and proper disposition of intracellular organelles deputed to Ca2+ handling and aerobic production of ATP is challenged by reduced activity; hence, modifications in the architecture of these intracellular membrane systems and organelles may contribute to muscle dysfunction in ageing and sarcopenia Keywords: Excitation–Contraction (EC) coupling; Mitochondria; Store-Operated Calcium Entry (SOCE); Skeletal Muscle.
