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Mitochondrial Ca2+ uniporter and CaMKII in heart

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Abstract

Arising from M. A. Joiner et al. Nature 491, 269–273 (2012); doi:10.1038/nature1023410.1038/nature11444

The influx of cytosolic Ca2+ into mitochondria is mediated primarily by the mitochondrial calcium uniporter (MCU)1, a small-conductance, Ca2+-selective channel2,3,4,5,6—MCU modulates intracellular Ca2+ transients and regulates ATP production and cell death1. Recently, Joiner et al. reported that MCU is regulated by mitochondrial CaMKII, and this regulation determines stress response in heart7. They reported a very large current putatively mediated by MCU that was about two orders of magnitude greater than the MCU current (IMCU) that we previously measured in heart mitochondria3; furthermore, the current traces presented by Joiner et al. showed unusually high fluctuations incompatible with the low single-channel conductance of MCU. Here we performed patch-clamp recordings from mouse heart mitochondria under the exact conditions used by Joiner et al.7, and confirm that IMCU in cardiomyocytes is very small and is not directly regulated by CaMKII; thus, the currents presented by Joiner et al. do not appear to correspond to MCU, and there is no direct electrophysiological evidence that CaMKII regulates MCU. There is a Reply to this Brief Communication Arising by Joiner, M. A. et al. Nature 513, http://dx.doi.org/10.1038/nature13627 (2014).

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Figure 1: Heart MCU current and CaMKII.

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Authors and Affiliations

  1. Department of Physiology, University of California San Francisco, San Francisco, 94158, California, USA

    Francesca Fieni & Yuriy Kirichok

  2. Department of Biochemistry and Molecular Biology, Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, 46202, Indiana, USA

    Derrick E. Johnson & Andy Hudmon

Authors
  1. Francesca Fieni
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  2. Derrick E. Johnson
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  3. Andy Hudmon
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  4. Yuriy Kirichok
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Contributions

F.F. and Y.K. conceived the project. F.F. performed electrophysiological experiments. D.E.J. and A.H. generated recombinant CAMKII and determined its activity under various conditions. All authors contributed to experimental design, discussed the results, and wrote the manuscript.

Corresponding author

Correspondence to Yuriy Kirichok.

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Declared none.

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Fieni, F., Johnson, D., Hudmon, A. et al. Mitochondrial Ca2+ uniporter and CaMKII in heart. Nature 513, E1–E2 (2014). https://doi.org/10.1038/nature13626

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