title: The ins and outs of mitochondrial calcium.
abstract: Calcium is thought to play an important role in regulating mitochondrial function. Evidence suggests that an increase in mitochondrial calcium can augment ATP production by altering the activity of calcium-sensitive mitochondrial matrix enzymes. In contrast, the entry of large amounts of mitochondrial calcium in the setting of ischemia-reperfusion injury is thought to be a critical event in triggering cellular necrosis. For many decades, the details of how calcium entered the mitochondria remained a biological mystery. In the past few years, significant progress has been made in identifying the molecular components of the mitochondrial calcium uniporter complex. Here, we review how calcium enters and leaves the mitochondria, the growing insight into the topology, stoichiometry and function of the uniporter complex, and the early lessons learned from some initial mouse models that genetically perturb mitochondrial calcium homeostasis.
authors.affiliation: From the Center for Molecular Medicine (T.F., K.M.H., Julia Liu, Jie Liu) and Systems Biology Center (S.M., R.J.P., J.S., E.M.), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD; and Laboratory of Cell Biology, National Center of Biomedical Analysis, Beijing, China (X.P.). finkelt@nih.gov murphy1@mail.nih.gov.
authors.forename: Toren
authors.initials: T
authors.lastname: Finkel
authors.affiliation: From the Center for Molecular Medicine (T.F., K.M.H., Julia Liu, Jie Liu) and Systems Biology Center (S.M., R.J.P., J.S., E.M.), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD; and Laboratory of Cell Biology, National Center of Biomedical Analysis, Beijing, China (X.P.).
authors.forename: Sara
authors.initials: S
authors.lastname: Menazza
authors.affiliation: From the Center for Molecular Medicine (T.F., K.M.H., Julia Liu, Jie Liu) and Systems Biology Center (S.M., R.J.P., J.S., E.M.), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD; and Laboratory of Cell Biology, National Center of Biomedical Analysis, Beijing, China (X.P.).
authors.forename: Kira M
authors.initials: KM
authors.lastname: Holmström
authors.affiliation: From the Center for Molecular Medicine (T.F., K.M.H., Julia Liu, Jie Liu) and Systems Biology Center (S.M., R.J.P., J.S., E.M.), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD; and Laboratory of Cell Biology, National Center of Biomedical Analysis, Beijing, China (X.P.).
authors.forename: Randi J
authors.initials: RJ
authors.lastname: Parks
authors.affiliation: From the Center for Molecular Medicine (T.F., K.M.H., Julia Liu, Jie Liu) and Systems Biology Center (S.M., R.J.P., J.S., E.M.), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD; and Laboratory of Cell Biology, National Center of Biomedical Analysis, Beijing, China (X.P.).
authors.forename: Julia
authors.initials: J
authors.lastname: Liu
authors.affiliation: From the Center for Molecular Medicine (T.F., K.M.H., Julia Liu, Jie Liu) and Systems Biology Center (S.M., R.J.P., J.S., E.M.), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD; and Laboratory of Cell Biology, National Center of Biomedical Analysis, Beijing, China (X.P.).
authors.forename: Junhui
authors.initials: J
authors.lastname: Sun
authors.affiliation: From the Center for Molecular Medicine (T.F., K.M.H., Julia Liu, Jie Liu) and Systems Biology Center (S.M., R.J.P., J.S., E.M.), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD; and Laboratory of Cell Biology, National Center of Biomedical Analysis, Beijing, China (X.P.).
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: From the Center for Molecular Medicine (T.F., K.M.H., Julia Liu, Jie Liu) and Systems Biology Center (S.M., R.J.P., J.S., E.M.), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD; and Laboratory of Cell Biology, National Center of Biomedical Analysis, Beijing, China (X.P.).
authors.forename: Xin
authors.initials: X
authors.lastname: Pan
authors.affiliation: From the Center for Molecular Medicine (T.F., K.M.H., Julia Liu, Jie Liu) and Systems Biology Center (S.M., R.J.P., J.S., E.M.), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD; and Laboratory of Cell Biology, National Center of Biomedical Analysis, Beijing, China (X.P.). finkelt@nih.gov murphy1@mail.nih.gov.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Murphy
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D006801:Humans; D017136:Ion Transport; D008928:Mitochondria / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D008954:Models, Biological
chemical_list: D015220:Calcium Channels; D024101:Mitochondrial Proteins; C034703:mitochondrial calcium uniporter; D000255:Adenosine Triphosphate; D002118:Calcium
keywords: calcium signaling; cell death; mitochondria