Letter abstract


Nature Cell Biology 9, 445 - 452 (2007)
Published online: 11 March 2007 | Corrected online: 16 October 2008 | doi:10.1038/ncb1556



There is a Corrigendum (November 2008) associated with this Letter.

Uncoupling proteins 2 and 3 are fundamental for mitochondrial Ca2+ uniport

Michael Trenker1,2, Roland Malli1,2, Ismene Fertschai1, Sanja Levak-Frank1 & Wolfgang F. Graier1,2

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Mitochondrial Ca2+ uptake is crucial for the regulation of the rate of oxidative phosphorylation1, the modulation of spatio-temporal cytosolic Ca2+ signals2, 3, 4 and apoptosis5. Although the phenomenon of mitochondrial Ca2+ sequestration, its characteristics and physiological consequences have been convincingly reported6, 7, the actual protein(s) involved in this process are unknown. Here, we show that the uncoupling proteins 2 and 3 (UCP2 and UCP3) are essential for mitochondrial Ca2+ uptake. Using overexpression, knockdown (small interfering RNA) and mutagenesis experiments, we demonstrate that UCP2 and UCP3 are elementary for mitochondrial Ca2+ sequestration in response to cell stimulation under physiological conditions — observations supported by isolated liver mitochondria of Ucp2-/- mice lacking ruthenium red-sensitive Ca2+ uptake. Our results reveal a novel molecular function for UCP2 and UCP3, and may provide the molecular mechanism for their reported effects8, 9, 10. Moreover, the identification of proteins fundemental for mitochondrial Ca2+ uptake expands our knowledge of the physiological role for mitochondrial Ca2+ sequestration.

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  1. Institute of Molecular Biology and Biochemistry, Centre of Molecular Medicine, Medical University of Graz, Harrachgasse 21/III, 8010 Graz, Austria.
  2. These authors contributed equally to this work.

Correspondence to: Wolfgang F. Graier1,2 e-mail: wolfgang.graier@meduni-graz.at

* In the version of this article initially published, the third and fifth histogram columns in the right panel of Fig. 2a were incorrectly labelled. The third column should have been siUCP3 and the fifth should have been siUPC2. These errors have been corrected in the HTML and PDF versions of the article.

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