The physiological role of mitochondrial calcium revealed by mice lacking the mitochondrial calcium uniporter (MCU)
By Xin Pan, Jie Liu, T. Nguyen, Chengyu Liu, Junhui Sun, Yanjie Teng, M. Fergusson, I. Rovira, Michele D. Allen, D. Springer and 5 more. Nature Cell Biology, 2013
664 citations recorded by the source corpus.
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.
Subfields: Molecular Biology, Physiology
View Paper: https://www.semanticscholar.org/paper/def78002aa83b0ee0dcc9d46db0f00d0ff72ad7a
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Citations in the corpus
- Essential versus accessory aspects of cell death: recommendations of the NCCD 2015 (2014, background): “Perhaps, the central role of CYPD in MPT-driven RCD reflects its ability to control the Ca2þ buffering capacity of the mitochondrial network.(235,236) This hypothesis has not yet been formally addressed.”
- Mitochondrial dysfunction in pathophysiology of heart failure (2018, background): “5 but are viable and grossly normal on mixed backgrounds (100).”