title: Mitochondrial calcium uniporter regulator 1 (MCUR1) regulates the calcium threshold for the mitochondrial permeability transition.
abstract: During the mitochondrial permeability transition, a large channel in the inner mitochondrial membrane opens, leading to the loss of multiple mitochondrial solutes and cell death. Key triggers include excessive reactive oxygen species and mitochondrial calcium overload, factors implicated in neuronal and cardiac pathophysiology. Examining the differential behavior of mitochondrial Ca(2+) overload in Drosophila versus human cells allowed us to identify a gene, MCUR1, which, when expressed in Drosophila cells, conferred permeability transition sensitive to electrophoretic Ca(2+) uptake. Conversely, inhibiting MCUR1 in mammalian cells increased the Ca(2+) threshold for inducing permeability transition. The effect was specific to the permeability transition induced by Ca(2+), and such resistance to overload translated into improved cell survival. Thus, MCUR1 expression regulates the Ca(2+) threshold required for permeability transition.
authors.affiliation: Howard Hughes Medical Institute, Department of Cardiology, Boston Children's Hospital, Boston, MA 02115;
authors.forename: Dipayan
authors.identifier: http://orcid.org/0000-0003-0605-7334
authors.initials: D
authors.lastname: Chaudhuri
authors.affiliation: Harvard University, Cambridge, MA 02138;
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Artiga
authors.affiliation: Howard Hughes Medical Institute, Department of Cardiology, Boston Children's Hospital, Boston, MA 02115;
authors.forename: Sunday A
authors.initials: SA
authors.lastname: Abiria
authors.affiliation: Howard Hughes Medical Institute, Department of Cardiology, Boston Children's Hospital, Boston, MA 02115; Department of Neurobiology, Harvard Medical School, Boston, MA 02115 dclapham@enders.tch.harvard.edu.
authors.forename: David E
authors.initials: DE
authors.lastname: Clapham
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D021983:Cyclophilins / Q000235:genetics / Q000378:metabolism; D004330:Drosophila / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D005452:Fluoresceins / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D010539:Permeability; D051381:Rats; D017386:Sequence Homology, Amino Acid; D000097322:Peptidyl-Prolyl Isomerase D
chemical_list: D002118:Calcium; D021983:Cyclophilins; D029721:Drosophila Proteins; D005452:Fluoresceins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C000601188:MCUR1 protein, human; C114456:PPID protein, human; D000097322:Peptidyl-Prolyl Isomerase D; C007740:fluorexon
keywords: Drosophila; H9C2; MCU; cyclophilin D; uniporter