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 language | English |
|---|---|
| Pages (from-to) | E1-E2 |
| Journal | Nature |
| Volume | 513 |
| Issue number | 7519 |
| DOIs | |
| State | Published - Sep 25 2015 |
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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 journal › Article
}
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
VL - 513
SP - E1-E2
JO - Nature
JF - Nature
SN - 0028-0836
IS - 7519
ER -