Assessment of cardiac function in mice lacking the mitochondrial calcium uniporter

Kira M. Holmström, Xin Pan, Julia C. Liu, Sara Menazza, Jie Liu, Tiffany T. Nguyen, Haihui Pan, Randi J. Parks, Stasia Anderson, Audrey Noguchi, Danielle Springer, Elizabeth Murphy, Toren Finkel

Research output: Contribution to journalArticle

Abstract

Mitochondrial calcium is thought to play an important role in the regulation of cardiac bioenergetics and function. The entry of calcium into the mitochondrial matrix requires that the divalent cation pass through the inner mitochondrial membrane via a specialized pore known as the mitochondrial calcium uniporter (MCU). Here, we use mice deficient of MCU expression to rigorously assess the role of mitochondrial calcium in cardiac function. Mitochondria isolated from MCU-/- mice have reduced matrix calcium levels, impaired calcium uptake and a defect in calcium-stimulated respiration. Nonetheless, we find that the absence of MCU expression does not affect basal cardiac function at either 12 or 20months of age. Moreover, the physiological response of MCU-/- mice to isoproterenol challenge or transverse aortic constriction appears similar to control mice. Thus, while mitochondria derived from MCU-/- mice have markedly impaired mitochondrial calcium handling, the hearts of these animals surprisingly appear to function relatively normally under basal conditions and during stress.

Original languageEnglish (US)
Pages (from-to)178-182
Number of pages5
JournalJournal of Molecular and Cellular Cardiology
Volume85
DOIs
StatePublished - Aug 1 2015
Externally publishedYes

Keywords

  • Bioenergetics
  • Calcium
  • Cardiac function
  • Mitochondria

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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  • Cite this

    Holmström, K. M., Pan, X., Liu, J. C., Menazza, S., Liu, J., Nguyen, T. T., Pan, H., Parks, R. J., Anderson, S., Noguchi, A., Springer, D., Murphy, E., & Finkel, T. (2015). Assessment of cardiac function in mice lacking the mitochondrial calcium uniporter. Journal of Molecular and Cellular Cardiology, 85, 178-182. https://doi.org/10.1016/j.yjmcc.2015.05.022