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http://purl.uniprot.org/citations/21685888http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/21685888http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/21685888http://www.w3.org/2000/01/rdf-schema#comment"Mitochondrial Ca(2+) homeostasis has a key role in the regulation of aerobic metabolism and cell survival, but the molecular identity of the Ca(2+) channel, the mitochondrial calcium uniporter, is still unknown. Here we have identified in silico a protein (named MCU) that shares tissue distribution with MICU1 (also known as CBARA1), a recently characterized uniporter regulator, is present in organisms in which mitochondrial Ca(2+) uptake was demonstrated and whose sequence includes two transmembrane domains. Short interfering RNA (siRNA) silencing of MCU in HeLa cells markedly reduced mitochondrial Ca(2+) uptake. MCU overexpression doubled the matrix Ca(2+) concentration increase evoked by inositol 1,4,5-trisphosphate-generating agonists, thus significantly buffering the cytosolic elevation. The purified MCU protein showed channel activity in planar lipid bilayers, with electrophysiological properties and inhibitor sensitivity of the uniporter. A mutant MCU, in which two negatively charged residues of the putative pore-forming region were replaced, had no channel activity and reduced agonist-dependent matrix Ca(2+) concentration transients when overexpressed in HeLa cells. Overall, these data demonstrate that the 40-kDa protein identified is the channel responsible for ruthenium-red-sensitive mitochondrial Ca(2+) uptake, thus providing a molecular basis for this process of utmost physiological and pathological relevance."xsd:string
http://purl.uniprot.org/citations/21685888http://purl.org/dc/terms/identifier"doi:10.1038/nature10230"xsd:string
http://purl.uniprot.org/citations/21685888http://purl.org/dc/terms/identifier"doi:10.1038/nature10230"xsd:string
http://purl.uniprot.org/citations/21685888http://purl.uniprot.org/core/author"Rizzuto R."xsd:string
http://purl.uniprot.org/citations/21685888http://purl.uniprot.org/core/author"Rizzuto R."xsd:string
http://purl.uniprot.org/citations/21685888http://purl.uniprot.org/core/author"Szabo I."xsd:string
http://purl.uniprot.org/citations/21685888http://purl.uniprot.org/core/author"Szabo I."xsd:string
http://purl.uniprot.org/citations/21685888http://purl.uniprot.org/core/author"De Stefani D."xsd:string
http://purl.uniprot.org/citations/21685888http://purl.uniprot.org/core/author"De Stefani D."xsd:string
http://purl.uniprot.org/citations/21685888http://purl.uniprot.org/core/author"Teardo E."xsd:string
http://purl.uniprot.org/citations/21685888http://purl.uniprot.org/core/author"Teardo E."xsd:string
http://purl.uniprot.org/citations/21685888http://purl.uniprot.org/core/author"Raffaello A."xsd:string
http://purl.uniprot.org/citations/21685888http://purl.uniprot.org/core/author"Raffaello A."xsd:string
http://purl.uniprot.org/citations/21685888http://purl.uniprot.org/core/date"2011"xsd:gYear
http://purl.uniprot.org/citations/21685888http://purl.uniprot.org/core/date"2011"xsd:gYear
http://purl.uniprot.org/citations/21685888http://purl.uniprot.org/core/name"Nature"xsd:string
http://purl.uniprot.org/citations/21685888http://purl.uniprot.org/core/name"Nature"xsd:string
http://purl.uniprot.org/citations/21685888http://purl.uniprot.org/core/pages"336-340"xsd:string
http://purl.uniprot.org/citations/21685888http://purl.uniprot.org/core/pages"336-340"xsd:string
http://purl.uniprot.org/citations/21685888http://purl.uniprot.org/core/title"A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter."xsd:string
http://purl.uniprot.org/citations/21685888http://purl.uniprot.org/core/title"A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter."xsd:string
http://purl.uniprot.org/citations/21685888http://purl.uniprot.org/core/volume"476"xsd:string
http://purl.uniprot.org/citations/21685888http://purl.uniprot.org/core/volume"476"xsd:string