Mitochondrial Ca<sup>2+</sup> uniporter and CaMKII in heart

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

Research output: Contribution to journalArticle

24 Citations (Scopus)

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
Pages (from-to)E1-E2
JournalNature
Volume513
Issue number7519
DOIs
StatePublished - Sep 25 2015

Fingerprint

Calcium-Calmodulin-Dependent Protein Kinase Type 2
Heart Mitochondria
mitochondrial calcium uniporter
Cardiac Myocytes
Mitochondria
Cell Death
Adenosine Triphosphate

ASJC Scopus subject areas

  • General

Cite this

Mitochondrial Ca<sup>2+</sup> uniporter and CaMKII in heart. / Fieni, Francesca; Johnson, Derrick E.; Hudmon, Andy; Kirichok, Yuriy.

In: Nature, Vol. 513, No. 7519, 25.09.2015, p. E1-E2.

Research output: Contribution to journalArticle

Fieni, F, Johnson, DE, Hudmon, A & Kirichok, Y 2015, 'Mitochondrial Ca<sup>2+</sup> uniporter and CaMKII in heart', Nature, vol. 513, no. 7519, pp. E1-E2. https://doi.org/10.1038/nature13626
Fieni, Francesca ; Johnson, Derrick E. ; Hudmon, Andy ; Kirichok, Yuriy. / Mitochondrial Ca<sup>2+</sup> uniporter and CaMKII in heart. In: Nature. 2015 ; Vol. 513, No. 7519. pp. E1-E2.
@article{412e31c08eab4a379fc54fefbb34de64,
title = "Mitochondrial Ca2+ uniporter and CaMKII in heart",
abstract = "The influx of cytosolic Ca2+ into mitochondria is mediated primarily by the mitochondrial calcium uniporter (MCU), a small-conductance, Ca2+ -selective channel - MCU modulates intracellular Ca2+ 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 (IMCU) 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 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).",
author = "Francesca Fieni and Johnson, {Derrick E.} and Andy Hudmon and Yuriy Kirichok",
year = "2015",
month = "9",
day = "25",
doi = "10.1038/nature13626",
language = "English",
volume = "513",
pages = "E1--E2",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7519",

}

TY - JOUR

T1 - Mitochondrial Ca2+ uniporter and CaMKII in heart

AU - Fieni, Francesca

AU - Johnson, Derrick E.

AU - Hudmon, Andy

AU - Kirichok, Yuriy

PY - 2015/9/25

Y1 - 2015/9/25

N2 - The influx of cytosolic Ca2+ into mitochondria is mediated primarily by the mitochondrial calcium uniporter (MCU), a small-conductance, Ca2+ -selective channel - MCU modulates intracellular Ca2+ 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 (IMCU) 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 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).

AB - The influx of cytosolic Ca2+ into mitochondria is mediated primarily by the mitochondrial calcium uniporter (MCU), a small-conductance, Ca2+ -selective channel - MCU modulates intracellular Ca2+ 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 (IMCU) 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 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).

UR - http://www.scopus.com/inward/record.url?scp=84908509852&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84908509852&partnerID=8YFLogxK

U2 - 10.1038/nature13626

DO - 10.1038/nature13626

M3 - Article

C2 - 25254480

AN - SCOPUS:84908509852

VL - 513

SP - E1-E2

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7519

ER -