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

Xin Pan, Jie Liu, Tiffany Nguyen, Chengyu Liu, Junhui Sun, Yanjie Teng, Maria M. Fergusson, Ilsa I. Rovira, Michele Allen, Danielle A. Springer, Angel M. Aponte, Marjan Gucek, Robert S. Balaban, Elizabeth Murphy, Toren Finkel

Research output: Contribution to journalArticle

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 languageEnglish (US)
JournalNature Cell Biology
DOIs
StateAccepted/In press - Nov 10 2013
Externally publishedYes

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Calcium
Permeability
Mitochondria
Cell Death
Basal Metabolism
mitochondrial calcium uniporter
Pyruvic Acid
Energy Metabolism
Oxidoreductases
Skeletal Muscle
Phosphorylation

ASJC Scopus subject areas

  • Cell Biology

Cite this

The physiological role of mitochondrial calcium revealed by mice lacking the mitochondrial calcium uniporter. / Pan, Xin; Liu, Jie; Nguyen, Tiffany; Liu, Chengyu; Sun, Junhui; Teng, Yanjie; Fergusson, Maria M.; Rovira, Ilsa I.; Allen, Michele; Springer, Danielle A.; Aponte, Angel M.; Gucek, Marjan; Balaban, Robert S.; Murphy, Elizabeth; Finkel, Toren.

In: Nature Cell Biology, 10.11.2013.

Research output: Contribution to journalArticle

Pan, X, Liu, J, Nguyen, T, Liu, C, Sun, J, Teng, Y, Fergusson, MM, Rovira, II, Allen, M, Springer, DA, Aponte, AM, Gucek, M, Balaban, RS, Murphy, E & Finkel, T 2013, 'The physiological role of mitochondrial calcium revealed by mice lacking the mitochondrial calcium uniporter', Nature Cell Biology. https://doi.org/10.1038/ncb2868
Pan, Xin ; Liu, Jie ; Nguyen, Tiffany ; Liu, Chengyu ; Sun, Junhui ; Teng, Yanjie ; Fergusson, Maria M. ; Rovira, Ilsa I. ; Allen, Michele ; Springer, Danielle A. ; Aponte, Angel M. ; Gucek, Marjan ; Balaban, Robert S. ; Murphy, Elizabeth ; Finkel, Toren. / The physiological role of mitochondrial calcium revealed by mice lacking the mitochondrial calcium uniporter. In: Nature Cell Biology. 2013.
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