title: Mitochondrial Ca(2+) uptake in skeletal muscle health and disease.
abstract: 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.
authors.affiliation: Kansas City University of Medicine and Bioscience, Dybedal Research Center, Kansas City, MO, 64106, USA. jzhou@kcumb.edu.
authors.forename: Jingsong
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Kansas City University of Medicine and Bioscience, Dybedal Research Center, Kansas City, MO, 64106, USA.
authors.forename: Kamal
authors.initials: K
authors.lastname: Dhakal
authors.affiliation: Kansas City University of Medicine and Bioscience, Dybedal Research Center, Kansas City, MO, 64106, USA.
authors.forename: Jianxun
authors.initials: J
authors.lastname: Yi
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000493:pharmacokinetics; D056966:Excitation Contraction Coupling; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D008931:Mitochondria, Muscle / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000502:physiology; D009135:Muscular Diseases / Q000378:metabolism* / Q000503:physiopathology; D009469:Neuromuscular Junction / Q000378:metabolism / Q000502:physiology / Q000503:physiopathology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
chemical_list: D002118:Calcium
keywords: Ca2+; mitochondria; skeletal muscle