Trenker 2007 Nat Cell Biol

Trenker M, Malli R, Fertschai I, Levak-Frank S, Graier WF (2007) Uncoupling proteins 2 and 3 are fundamental for mitochondrial Ca2+ uniport. Nat Cell Biol 9:445-52.

» PMID: 17351641 Open Access

Trenker Michael, Malli Roland, Fertschai Ismene, Levak-Frank Sanja, Graier Wolfgang (2007) Nat Cell Biol

Abstract: Mitochondrial Ca(2+) uptake is crucial for the regulation of the rate of oxidative phosphorylation, the modulation of spatio-temporal cytosolic Ca(2+) signals and apoptosis. Although the phenomenon of mitochondrial Ca(2+) sequestration, its characteristics and physiological consequences have been convincingly reported, 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 Ca(2+) uptake. Using overexpression, knockdown (small interfering RNA) and mutagenesis experiments, we demonstrate that UCP2 and UCP3 are elementary for mitochondrial Ca(2+) sequestration in response to cell stimulation under physiological conditions - observations supported by isolated liver mitochondria of Ucp2(-/-) mice lacking ruthenium red-sensitive Ca(2+) uptake. Our results reveal a novel molecular function for UCP2 and UCP3, and may provide the molecular mechanism for their reported effects. Moreover, the identification of proteins fundemental for mitochondrial Ca(2+) uptake expands our knowledge of the physiological role for mitochondrial Ca(2+) sequestration.

• Bioblast editor: Cecatto C • O2k-Network Lab: AT Graz Graier W

Labels: MiParea: Genetic knockout;overexpression 

Organism: Mouse, Saccharomyces cerevisiae  Tissue;cell: Liver, Other cell lines, CHO, HeLa  Preparation: Isolated mitochondria 

Regulation: ATP production, Calcium, Ion;substrate transport 

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