The In Vivo Biology of the Mitochondrial Calcium Uniporter

Julia C Liu; Randi J Parks; Jie Liu; Justin Stares; Ilsa I Rovira; Elizabeth Murphy; Toren Finkel

doi:10.1007/978-3-319-55330-6_3

The In Vivo Biology of the Mitochondrial Calcium Uniporter

Adv Exp Med Biol. 2017:982:49-63. doi: 10.1007/978-3-319-55330-6_3.

Authors

Julia C Liu¹, Randi J Parks², Jie Liu¹, Justin Stares¹, Ilsa I Rovira¹, Elizabeth Murphy², Toren Finkel^{3

4}

Affiliations

¹ Center for Molecular Medicine, National Heart Lung and Blood Institute, Bethesda, MD, 20892, USA.
² Systems Biology Center, National Heart Lung and Blood Institute, Bethesda, MD, 20892, USA.
³ Center for Molecular Medicine, National Heart Lung and Blood Institute, Bethesda, MD, 20892, USA. finkelt@nih.gov.
⁴ NIH, Bldg 10/CRC 5-3330, Bethesda, MD, 20892, USA. finkelt@nih.gov.

PMID: 28551781
DOI: 10.1007/978-3-319-55330-6_3

Abstract

The identification of the molecular composition of the mitochondrial calcium uniporter has allowed for the genetic manipulation of its components and the creation of various in vivo genetic models. Here, we review the initial attempts to modulate the expression of components of the calcium uniporter in a range of organisms from plants to mammals. This analysis has confirmed the strict requirement for the uniporter for in vivo mitochondrial calcium uptake and for maintaining mitochondrial calcium homeostasis. We further discuss the physiological effects following genetic manipulation of the uniporter on tissue bioenergetics and the threshold for cell death. Finally, we analyze the limited information regarding the role of various uniporter components in human disease.

Keywords: MCU; Mitochondrial calcium; Model organisms; Mouse models; Uniporter.

Publication types

Review

MeSH terms

Adenosine Triphosphate / metabolism
Animals
Calcium / metabolism*
Calcium Channels / chemistry
Calcium Channels / genetics
Calcium Channels / metabolism*
Calcium Signaling*
Calcium-Binding Proteins / chemistry
Calcium-Binding Proteins / genetics
Calcium-Binding Proteins / metabolism*
Cation Transport Proteins / chemistry
Cation Transport Proteins / genetics
Cation Transport Proteins / metabolism*
Cell Death
Energy Metabolism
Genotype
Humans
Mice, Knockout
Mitochondria / metabolism*
Mitochondria / pathology
Mitochondrial Membrane Transport Proteins / chemistry
Mitochondrial Membrane Transport Proteins / genetics
Mitochondrial Membrane Transport Proteins / metabolism*
Phenotype
Protein Conformation
Structure-Activity Relationship

Substances

Calcium Channels
Calcium-Binding Proteins
Cation Transport Proteins
MICU1 protein, human
MICU1 protein, mouse
Mitochondrial Membrane Transport Proteins
mitochondrial calcium uniporter
Adenosine Triphosphate
Calcium