The physiological role of mitochondrial calcium revealed by mice lacking the mitochondrial calcium uniporter (MCU)

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.

DOI: 10.1038/ncb2868

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@inproceedings{Pan2013ThePR, title={The physiological role of mitochondrial calcium revealed by mice lacking the mitochondrial calcium uniporter (MCU)}, author={Xin Pan and Jie Liu and Tiffany Tuyen M Nguyen and Chengyu Liu and Junhui Sun and Yanjie Teng and Maria M. Fergusson and Ilsa I. Rovira and Michele D. Allen and Danielle A. Springer and Angel Aponte and Marjan Gucek and Robert S Balaban and Elizabeth Jane Murphy and Toren Finkel}, booktitle={Nature Cell Biology}, year={2013} }