title: Assessment of cardiac function in mice lacking the mitochondrial calcium uniporter.
abstract: Mitochondrial calcium is thought to play an important role in the regulation of cardiac bioenergetics and function. The entry of calcium into the mitochondrial matrix requires that the divalent cation pass through the inner mitochondrial membrane via a specialized pore known as the mitochondrial calcium uniporter (MCU). Here, we use mice deficient of MCU expression to rigorously assess the role of mitochondrial calcium in cardiac function. Mitochondria isolated from MCU(-/-) mice have reduced matrix calcium levels, impaired calcium uptake and a defect in calcium-stimulated respiration. Nonetheless, we find that the absence of MCU expression does not affect basal cardiac function at either 12 or 20months of age. Moreover, the physiological response of MCU(-/-) mice to isoproterenol challenge or transverse aortic constriction appears similar to control mice. Thus, while mitochondria derived from MCU(-/-) mice have markedly impaired mitochondrial calcium handling, the hearts of these animals surprisingly appear to function relatively normally under basal conditions and during stress.
authors.affiliation: Center for Molecular Medicine, National Heart, Lung and Blood Institute, Bethesda, MD 20892, USA.
authors.forename: Kira M
authors.initials: KM
authors.lastname: Holmström
authors.affiliation: Center for Molecular Medicine, National Heart, Lung and Blood Institute, Bethesda, MD 20892, USA; Laboratory of Cell Biology, National Center of Biomedical Analysis, Beijing 100850, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Pan
authors.affiliation: Center for Molecular Medicine, National Heart, Lung and Blood Institute, Bethesda, MD 20892, USA.
authors.forename: Julia C
authors.initials: JC
authors.lastname: Liu
authors.affiliation: Systems Biology Center, National Heart, Lung and Blood Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Menazza
authors.affiliation: Center for Molecular Medicine, National Heart, Lung and Blood Institute, Bethesda, MD 20892, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Systems Biology Center, National Heart, Lung and Blood Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Tiffany T
authors.initials: TT
authors.lastname: Nguyen
authors.affiliation: Center for Molecular Medicine, National Heart, Lung and Blood Institute, Bethesda, MD 20892, USA.
authors.forename: Haihui
authors.initials: H
authors.lastname: Pan
authors.affiliation: Systems Biology Center, National Heart, Lung and Blood Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Randi J
authors.initials: RJ
authors.lastname: Parks
authors.affiliation: Animal MRI Core, National Heart, Lung and Blood Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Stasia
authors.initials: S
authors.lastname: Anderson
authors.affiliation: Murine Phenotyping Core, National Heart, Lung and Blood Institute, Bethesda, MD 20892, USA.
authors.forename: Audrey
authors.initials: A
authors.lastname: Noguchi
authors.affiliation: Murine Phenotyping Core, National Heart, Lung and Blood Institute, Bethesda, MD 20892, USA.
authors.forename: Danielle
authors.initials: D
authors.lastname: Springer
authors.affiliation: Systems Biology Center, National Heart, Lung and Blood Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Murphy
authors.affiliation: Center for Molecular Medicine, National Heart, Lung and Blood Institute, Bethesda, MD 20892, USA. Electronic address: finkelt@nih.gov.
authors.forename: Toren
authors.initials: T
authors.lastname: Finkel
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics* / Q000378:metabolism; D020013:Calcium Signaling; D005260:Female; D018345:Mice, Knockout; D008929:Mitochondria, Heart / Q000378:metabolism; D013318:Stroke Volume
chemical_list: D015220:Calcium Channels; C034703:mitochondrial calcium uniporter; D002118:Calcium
keywords: Bioenergetics; Calcium; Cardiac function; Mitochondria