title: Calcium signaling as a mediator of cell energy demand and a trigger to cell death.
abstract: Calcium signaling is pivotal to a host of physiological pathways. A rise in calcium concentration almost invariably signals an increased cellular energy demand. Consistent with this, calcium signals mediate a number of pathways that together serve to balance energy supply and demand. In pathological states, calcium signals can precipitate mitochondrial injury and cell death, especially when coupled to energy depletion and oxidative or nitrosative stress. This review explores the mechanisms that couple cell signaling pathways to metabolic regulation or to cell death. The significance of these pathways is exemplified by pathological case studies, such as those showing loss of mitochondrial calcium uptake 1 in patients and ischemia/reperfusion injury.
authors.affiliation: Department of Cell and Developmental Biology and Consortium for Mitochondrial Research, University College London, London, United Kingdom.
authors.forename: Gauri
authors.initials: G
authors.lastname: Bhosale
authors.affiliation: Department of Cell and Developmental Biology and Consortium for Mitochondrial Research, University College London, London, United Kingdom.
authors.forename: Jenny A
authors.initials: JA
authors.lastname: Sharpe
authors.affiliation: Department of Cell and Developmental Biology and Consortium for Mitochondrial Research, University College London, London, United Kingdom.
authors.forename: Stephanie Y
authors.initials: SY
authors.lastname: Sundier
authors.affiliation: Department of Cell and Developmental Biology and Consortium for Mitochondrial Research, University College London, London, United Kingdom.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Duchen
mesh_terms: D000818:Animals; D017209:Apoptosis; D020013:Calcium Signaling; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D016923:Cell Death; D004734:Energy Metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D009336:Necrosis; D010539:Permeability; D028061:Phosphate Transport Proteins / Q000235:genetics / Q000378:metabolism; D016062:Porosity
chemical_list: D002135:Calcium-Binding Proteins; D027682:Cation Transport Proteins; C116241:MICU1 protein, human; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D028061:Phosphate Transport Proteins; C422067:SLC25A3 protein, human
keywords: MICU1; calcium signaling; cell death; ischemia/reperfusion injury; mitochondrial calcium uptake; mitochondrial permeability transition pore