A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter (Articolo in rivista)

Type
Label
  • A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter (Articolo in rivista) (literal)
Anno
  • 2011-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1038/nature10230 (literal)
Alternative label
  • De Stefani, Diego; Raffaello, Anna; Teardo, Enrico; Szabo, Ildiko; Rizzuto, Rosario (2011)
    A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter
    in Nature (Lond.)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • De Stefani, Diego; Raffaello, Anna; Teardo, Enrico; Szabo, Ildiko; Rizzuto, Rosario (literal)
Pagina inizio
  • 336 (literal)
Pagina fine
  • U104 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 476 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#pagineTotali
  • 7 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 7360 (literal)
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • University of Padua; Consiglio Nazionale delle Ricerche (CNR); University of Padua (literal)
Titolo
  • A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter (literal)
Abstract
  • Mitochondrial Ca(2+) homeostasis has a key role in the regulation of aerobic metabolism and cell survival(1), but the molecular identity of the Ca(2+) channel, the mitochondrial calcium uniporter(2), 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(3), 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. (literal)
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