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Nat Cell Biol. 2013 Dec;15(12):1464-72. doi: 10.1038/ncb2868. Epub 2013 Nov 10.

The physiological role of mitochondrial calcium revealed by mice lacking the mitochondrial calcium uniporter.

Author information

1
1] Center for Molecular Medicine, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA [2] National Center of Biomedical Analysis, Beijing 100850, China [3].

Abstract

Mitochondrial calcium has been postulated to regulate a wide range of processes from bioenergetics to cell death. Here, we characterize a mouse model that lacks expression of the recently discovered mitochondrial calcium uniporter (MCU). Mitochondria derived from MCU(-/-) mice have no apparent capacity to rapidly uptake calcium. Whereas basal metabolism seems unaffected, the skeletal muscle of MCU(-/-) mice exhibited alterations in the phosphorylation and activity of pyruvate dehydrogenase. In addition, MCU(-/-) mice exhibited marked impairment in their ability to perform strenuous work. We further show that mitochondria from MCU(-/-) mice lacked evidence for calcium-induced permeability transition pore (PTP) opening. The lack of PTP opening does not seem to protect MCU(-/-) cells and tissues from cell death, although MCU(-/-) hearts fail to respond to the PTP inhibitor cyclosporin A. Taken together, these results clarify how acute alterations in mitochondrial matrix calcium can regulate mammalian physiology.

PMID:
24212091
PMCID:
PMC3852190
DOI:
10.1038/ncb2868
[Indexed for MEDLINE]
Free PMC Article

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