title: Enjoy the Trip: Calcium in Mitochondria Back and Forth.
abstract: In the last 5 years, most of the molecules that control mitochondrial Ca(2+) homeostasis have been finally identified. Mitochondrial Ca(2+) uptake is mediated by the Mitochondrial Calcium Uniporter (MCU) complex, a macromolecular structure that guarantees Ca(2+) accumulation inside mitochondrial matrix upon increases in cytosolic Ca(2+). Conversely, Ca(2+) release is under the control of the Na(+)/Ca(2+) exchanger, encoded by the NCLX gene, and of a H(+)/Ca(2+) antiporter, whose identity is still debated. The low affinity of the MCU complex, coupled to the activity of the efflux systems, protects cells from continuous futile cycles of Ca(2+) across the inner mitochondrial membrane and consequent massive energy dissipation. In this review, we discuss the basic principles that govern mitochondrial Ca(2+) homeostasis and the methods used to investigate the dynamics of Ca(2+) concentration within the organelles. We discuss the functional and structural role of the different molecules involved in mitochondrial Ca(2+) handling and their pathophysiological role.
authors.affiliation: Department of Biomedical Sciences, University of Padova, 35121 Padova, Italy; email: diego.destefani@unipd.it , rosario.rizzuto@unipd.it , tullio.pozzan@unipd.it.
authors.forename: Diego
authors.initials: D
authors.lastname: De Stefani
authors.affiliation: Department of Biomedical Sciences, University of Padova, 35121 Padova, Italy; email: diego.destefani@unipd.it , rosario.rizzuto@unipd.it , tullio.pozzan@unipd.it.|National Research Council (CNR) Neuroscience Institute, 35121 Padova, Italy.
authors.forename: Rosario
authors.initials: R
authors.lastname: Rizzuto
authors.affiliation: Department of Biomedical Sciences, University of Padova, 35121 Padova, Italy; email: diego.destefani@unipd.it , rosario.rizzuto@unipd.it , tullio.pozzan@unipd.it.|National Research Council (CNR) Neuroscience Institute, 35121 Padova, Italy.|Venetian Institute of Molecular Medicine, 35121 Padova, Italy.
authors.forename: Tullio
authors.initials: T
authors.lastname: Pozzan
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D017136:Ion Transport; D007700:Kinetics; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D051336:Mitochondrial Membranes / Q000378:metabolism / Q000648:ultrastructure; D024101:Mitochondrial Proteins; D008958:Models, Molecular; D019831:Sodium-Calcium Exchanger / Q000235:genetics / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D015220:Calcium Channels; D024101:Mitochondrial Proteins; C483046:SLC8B1 protein, human; D019831:Sodium-Calcium Exchanger; C034703:mitochondrial calcium uniporter; D002118:Calcium
keywords: Ca2+ signaling; MCU complex; NCLX