title: Molecular structure and pathophysiological roles of the Mitochondrial Calcium Uniporter.
abstract: Mitochondrial Ca(2+) uptake regulates a wide array of cell functions, from stimulation of aerobic metabolism and ATP production in physiological settings, to induction of cell death in pathological conditions. The molecular identity of the Mitochondrial Calcium Uniporter (MCU), the highly selective channel responsible for Ca(2+) entry through the IMM, has been described less than five years ago. Since then, research has been conducted to clarify the modulation of its activity, which relies on the dynamic interaction with regulatory proteins, and its contribution to the pathophysiology of organs and tissues. Particular attention has been placed on characterizing the role of MCU in cardiac and skeletal muscles. In this review we summarize the molecular structure and regulation of the MCU complex in addition to its pathophysiological role, with particular attention to striated muscle tissues. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou.
authors.affiliation: Department of Biomedical Sciences, University of Padua, 35131, Italy. Electronic address: cristina.mammucari@unipd.it.
authors.forename: Cristina
authors.initials: C
authors.lastname: Mammucari
authors.affiliation: Department of Biomedical Sciences, University of Padua, 35131, Italy. Electronic address: anna.raffaello@unipd.it.
authors.forename: Anna
authors.initials: A
authors.lastname: Raffaello
authors.affiliation: Department of Biomedical Sciences, University of Padua, 35131, Italy.
authors.forename: Denis
authors.initials: D
authors.lastname: Vecellio Reane
authors.affiliation: Department of Biomedical Sciences, University of Padua, 35131, Italy; Neuroscience Institute, National Research Council, Padua 35131, Italy. Electronic address: rosario.rizzuto@unipd.it.
authors.forename: Rosario
authors.initials: R
authors.lastname: Rizzuto
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000737:chemistry / Q000172:deficiency / Q000502:physiology*; D020013:Calcium Signaling; D002135:Calcium-Binding Proteins / Q000172:deficiency; D004195:Disease Models, Animal; D006801:Humans; D017136:Ion Transport / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008929:Mitochondria, Heart / Q000378:metabolism; D008931:Mitochondria, Muscle / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000235:genetics / Q000503:physiopathology; D033681:Mitochondrial Membrane Transport Proteins / Q000737:chemistry / Q000172:deficiency / Q000502:physiology*; D051336:Mitochondrial Membranes / Q000378:metabolism; D009124:Muscle Proteins / Q000737:chemistry / Q000502:physiology; D009928:Organ Specificity; D011487:Protein Conformation
chemical_list: D015220:Calcium Channels; D002135:Calcium-Binding Proteins; C000610715:MICU1 protein, mouse; D033681:Mitochondrial Membrane Transport Proteins; D009124:Muscle Proteins; C034703:mitochondrial calcium uniporter; D002118:Calcium
keywords: Cardiac muscle; Mitochondrial Calcium Uniporter; Mitochondrial calcium uptake; Skeletal muscle