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.
Original language | English (US) |
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Journal | Nature Cell Biology |
DOIs | |
State | Accepted/In press - Nov 10 2013 |
Externally published | Yes |
ASJC Scopus subject areas
- Cell Biology