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Review
. 2015 Apr;72(8):1489-98.
doi: 10.1007/s00018-014-1810-1. Epub 2014 Dec 30.

Molecular mechanism of mitochondrial calcium uptake

Lele Wang  1 , Xue Yang, Yuequan Shen
Affiliations
Review

Molecular mechanism of mitochondrial calcium uptake

Lele Wang et al. Cell Mol Life Sci. 2015 Apr.

Abstract

Mitochondrial calcium uptake plays a critical role in various cellular functions. After half a century of extensive studies, the molecular components and important regulators of the mitochondrial calcium uptake complex have been identified. However, the mechanism by which these protein molecules interact with one another and coordinate to regulate calcium passage through mitochondrial membranes remains elusive. Here, we summarize recent progress in the structural and functional characterization of these important protein molecules, which are involved in mitochondrial calcium uptake. In particular, we focus on the current understanding of the molecular mechanism underlying calcium through two mitochondrial membranes. Additionally, we provide a new perspective for future directions in investigation and molecular intervention.

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Figures

Fig. 1
Fig. 1
VDAC structure. a, b Cartoon representation of mouse VDAC (PDB code: 3EMN) with different perspectives. c Proposed Ca2+-binding sites in mouse VDAC. Residues E73 and E203 are shown as magenta spheres
Fig. 2
Fig. 2
Schematic representation of the mitochondrial calcium uptake complex in the low Ca2+ state (a) and high Ca2+ state (b). These models are based on our current understanding of the published data. IMM inner mitochondrial membrane
Fig. 3
Fig. 3
Conformational changes in human MICU1 upon Ca2+ binding. Cartoon representation of the overall MICU1 structure in the Ca2+-free (a) and Ca2+-bound states (b). PDB codes: 4NSC for the Ca2+-free MICU1 and 4NSD for the Ca2+-bound MICU1. Calcium is shown in red. c Potential MICU1 oligomer conversion upon Ca2+ binding. The Ca2+-free MICU1 hexamer is shown in red, blue, green, cyan, yellow and orange, respectively. The Ca2+-bound MICU1 dimer is shown in green and blue, respectively
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