The mutual relationship between mitochondrial structure and function is an emerging focus of biology and medicine. In the muscle, the Ca2+-driven contractile activity has to be dynamically matched by energy supply. Both Ca2+ homeostasis and energy metabolism rely on mitochondrial function. Based on recent evidence mitochondrial activity in ATP generation, in Ca2+ handling and even in cell death depends on continuous restructuring of the individual mitochondria in several cell types. Furthermore, Ca2+ the central regulator of muscle contraction emerges as a key signaling molecule in organellar dynamics. However, it has been difficult to study the mitochondrial fusion, fission and positioning in skeletal or cardiac muscle. Excitingly, recent advances in live cell microscopy and in the fluorescent protein technology provide a means to study mitochondrial dynamics and its signaling mechanisms in the muscle. The significance of these studies is further emphasized by the data on the possible mitochondrial contribution to human excitation contraction coupling diseases. We propose that mitochondrial morphology and dynamics are controlled by Ca2+ homeostasis in the muscle and become dysregulated and may contribute to tissue injury in genetic defects of the ryanodine receptors (RyRs), including malignant hyperthermia (MH) and catecholaminergic paroxysmal ventricular tachycardia (CPVT) causing mutations. The goal of my research is 1) To evaluate the mitochondrial network continuity in skeletal myotubes and cardiomyocyte primary cultures. 2). To test the hypothesis that the augmented Ca2+ release activity caused by RyR mutations alters mitochondrial morphology, fusion/fission and motility dynamics in muscle cells. 3) To test the mechanisms of the Ca2+ effect on mitochondrial dynamics under physiological and pathophysiological conditions in the muscle. 4) To evaluate the role of the physiological and pathological Ca2+-dependent changes on mitochondria morphology and dynamics in muscle cells bioenergetics and contractile function. This study will elucidate the possible mitochondrial contribution to human excitation-contraction coupling diseases, by clarifying the fundamental muscle mechanisms of mitochondrial dynamics and its relevance for Ca2+ homesotasis.