The mitochondrial uniporter controls fight or flight heart rate increases

Yuejin Wu, Tyler P. Rasmussen, Olha M. Koval, Mei Ling A. Joiner, Duane D. Hall, Biyi Chen, Elizabeth D. Luczak, Qiongling Wang, Adam G. Rokita, Xander H.T. Wehrens, Long Sheng Song, Mark E. Anderson

Research output: Contribution to journalArticlepeer-review

98 Scopus citations


Heart rate increases are a fundamental adaptation to physiological stress, while inappropriate heart rate increases are resistant to current therapies. However, the metabolic mechanisms driving heart rate acceleration in cardiac pacemaker cells remain incompletely understood. The mitochondrial calcium uniporter (MCU) facilitates calcium entry into the mitochondrial matrix to stimulate metabolism. We developed mice with myocardial MCU inhibition by transgenic expression of a dominant-negative (DN) MCU. Here, we show that DN-MCU mice had normal resting heart rates but were incapable of physiological fight or flight heart rate acceleration. We found that MCU function was essential for rapidly increasing mitochondrial calcium in pacemaker cells and that MCU-enhanced oxidative phoshorylation was required to accelerate reloading of an intracellular calcium compartment before each heartbeat. Our findings show that MCU is necessary for complete physiological heart rate acceleration and suggest that MCU inhibition could reduce inappropriate heart rate increases without affecting resting heart rate.

Original languageEnglish (US)
Article number6081
JournalNature communications
StatePublished - Jan 20 2015

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)


Dive into the research topics of 'The mitochondrial uniporter controls fight or flight heart rate increases'. Together they form a unique fingerprint.

Cite this