Mitochondrial Ca2+ uniporter and CaMKII in heart

Francesca Fieni, Derrick E. Johnson, Andy Hudmon, Yuriy Kirichok

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

The influx of cytosolic Ca<sup>2+</sup> into mitochondria is mediated primarily by the mitochondrial calcium uniporter (MCU), a small-conductance, Ca<sup>2+</sup> -selective channel - MCU modulates intracellular Ca<sup>2+</sup> transients and regulates ATP production and cell death. Recently, Joiner et al. reported that MCU is regulated by mitochondrial CaMKII, and this regulation determines stress response in heart. They reported a very large current putatively mediated by MCU that was about two orders of magnitude greater than the MCU current (I<inf>MCU</inf>) that we previously measured in heart mitochondria; 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., and confirm that I<inf>MCU</inf> 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).

Original languageEnglish (US)
Pages (from-to)E1-E2
JournalNature
Volume513
Issue number7519
DOIs
StatePublished - Sep 25 2014

ASJC Scopus subject areas

  • General

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    Fieni, F., Johnson, D. E., Hudmon, A., & Kirichok, Y. (2014). Mitochondrial Ca2+ uniporter and CaMKII in heart. Nature, 513(7519), E1-E2. https://doi.org/10.1038/nature13626