Mitochondrial Ca^(2+) uptake in skeletal muscle health and disease

Muscle uses Ca2＋ as a messenger to control contraction and relies on ATP to maintain the intracellular Ca2＋ homeostasis. Mi- tochondria are the major sub-cellular organelle of ATP production. With a negative inner membrane potential, mitochondria take up Ca2＋ from their surroundings, a process called mitochondrial Ca2＋ uptake. Under physiological conditions, Ca2＋ uptake into mitochondria promotes ATP production. Excessive uptake causes mitochondrial Ca2＋ overload, which activates down- stream adverse responses leading to cell dysfunction. Moreover, mitochondrial Ca2＋ uptake could shape spatio-temporal pat- terns of intracellular Ca〉 signaling. Malfunction of mitochondrial Ca2＋ uptake is implicated in muscle degeneration. Unlike non-excitable cells, mitochondria in muscle cells experience dramatic changes of intracellular Ca2＋ levels. Besides the sudden elevation of Ca2＋ level induced by action potentials, Ca2＋ transients in muscle cells can be as short as a few milliseconds during a single twitch or as long as minutes during tetanic contraction, which raises the question whether mitochondrial Ca2＋ uptake is fast and big enough to shape intracellular Ca2＋ signaling during excitation-contraction coupling and creates technical challeng- es for quantification of the dynamic changes of Ca2＋ inside mitochondria. This review focuses on characterization of mito- chondrial Ca2＋ uptake in skeletal muscle and its role in muscle physiology and diseases.

Muscle uses Ca^(2+) as a messenger to control contraction and relies on ATP to maintain the intracellular Ca^(2+) homeostasis. Mitochondria are the major sub-cellular organelle of ATP production. With a negative inner membrane potential, mitochondria take up Ca^(2+) from their surroundings, a process called mitochondrial Ca^(2+) uptake. Under physiological conditions, Ca^(2+) uptake into mitochondria promotes ATP production. Excessive uptake causes mitochondrial Ca^(2+) overload, which activates downstream adverse responses leading to cell dysfunction. Moreover, mitochondrial Ca^(2+) uptake could shape spatio-temporal patterns of intracellular Ca^(2+) signaling. Malfunction of mitochondrial Ca^(2+) uptake is implicated in muscle degeneration. Unlike non-excitable cells, mitochondria in muscle cells experience dramatic changes of intracellular Ca^(2+) levels. Besides the sudden elevation of Ca^(2+) level induced by action potentials, Ca^(2+) transients in muscle cells can be as short as a few milliseconds during a single twitch or as long as minutes during tetanic contraction, which raises the question whether mitochondrial Ca^(2+) uptake is fast and big enough to shape intracellular Ca^(2+) signaling during excitation-contraction coupling and creates technical challenges for quantification of the dynamic changes of Ca^(2+) inside mitochondria. This review focuses on characterization of mitochondrial Ca^(2+) uptake in skeletal muscle and its role in muscle physiology and diseases.