title: The mitochondrial calcium uniporter: mice can live and die without it.
abstract: Calcium is of critical importance to mitochondrial and cell function, and calcium signaling is highly localized in the cell. When stimulated, mitochondria are capable of rapidly taking up calcium, affecting both matrix energetics within mitochondria and shaping the amplitude and frequency of cytosolic calcium "waves". During pathological conditions a large increase in mitochondrial calcium levels is thought to activate the mitochondrial permeability transition pore, resulting in cell death. The protein responsible for mitochondrial calcium uptake, the mitochondrial calcium uniporter (MCU), was identified in 2011 and its molecular elucidation has stimulated and invigorated research in this area. MCU knockout mice have been created, a variety of other regulators have been identified, and a disease phenotype in humans has been attributed to the loss of a uniporter regulator. In the three years since its molecular elucidation, further research into the MCU has revealed a complex uniporter, and raised many questions about its physiologic and pathologic cell roles. This article is part of a Special Issue entitled "Mitochondria: From Basic Mitochondrial Biology to Cardiovascular Disease".
authors.affiliation: Systems Biology Center, NHLBI, NIH, Bethesda, MD, USA.
authors.forename: Josephine L
authors.initials: JL
authors.lastname: Harrington
authors.affiliation: Systems Biology Center, NHLBI, NIH, Bethesda, MD, USA. Electronic address: murphy1@mail.nih.gov.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Murphy
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling; D016923:Cell Death; D056726:Genetic Association Studies; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D033681:Mitochondrial Membrane Transport Proteins; C034703:mitochondrial calcium uniporter; D002118:Calcium
keywords: Calcium; Ischemia-reperfusion; Mitochondria; Mitochondrial permeability pore; Necrosis