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dc.contributor.author | Fuente, Sergio de la | - |
dc.contributor.author | Matesanz-Isabel, Jessica | - |
dc.contributor.author | Fonteriz, Rosalba I. | - |
dc.contributor.author | Montero, Mayte | - |
dc.contributor.author | Álvarez, Javier | - |
dc.date.accessioned | 2015-06-19T09:30:13Z | - |
dc.date.available | 2015-06-19T09:30:13Z | - |
dc.date.issued | 2014 | - |
dc.identifier | doi: 10.1042/BJ20131025 | - |
dc.identifier | issn: 0264-6021 | - |
dc.identifier | e-issn: 1470-8728 | - |
dc.identifier.citation | Biochemical Journal 458(1): 33-40 (2014) | - |
dc.identifier.uri | http://hdl.handle.net/10261/116870 | - |
dc.description.abstract | MICU1 (Ca2+ uptake protein 1, mitochondrial) is an important regulator of the MCU (Ca2+ uniporter protein, mitochondrial) that has been shown recently to act as a gatekeeper of the MCU at low [Ca2+]c (cytosolic [Ca2+]). In the present study we have investigated in detail the dynamics of MCU activity after shRNA-knockdown of MICU1 and we have found several new interesting properties. In MICU1-knockdown cells, the rate of mitochondrial Ca2+ uptake was largely increased at a low [Ca2+]c (<2 μM), but it was decreased at a high [Ca2+]c (>4 μM). In the 2-4 μM range a mixed behaviour was observed, where mitochondrial Ca2+ uptake started earlier in the MICU1-silenced cells, but at a lower rate than in the controls. The sensitivity of Ca2+ uptake to Ruthenium Red and Ru360 was similar at both high and low [Ca2+]c, indicating that the same Ca2+ pathway was operating in both cases. The increased Ca2+-uptake rate observed at a [Ca2+]c below 2 μM was transient and became inhibited during Ca2+ entry. Development of this inhibition was slow, requiring 5 min for completion, and was hardly reversible. Therefore MICU1 acts both as a MCU gatekeeper at low [Ca2+]c and as a cofactor necessary to reach the maximum Ca2+-uptake rate at high [Ca2+]c. Moreover, in the absence of MICU1, the MCU becomes sensitive to a slow-developing inhibition that requires prolonged increases in [Ca2+]c in the low micromolar range. | - |
dc.description.sponsorship | This work was supported by the spanish Ministerio de Ciencia e Innovación [grant number BFU2011-25763], the Junta de Castilla y León [grant number VA029A12-1] and the Spanish Government via FPI (Formación de Personal Investigador) fellowships (to S.D.L.F. and J.M.-I.). | - |
dc.publisher | Biochemical Society | - |
dc.rights | closedAccess | - |
dc.title | Dynamics of mitochondrial Ca2+ uptake in MICU1-knockdown cells | - |
dc.type | artículo | - |
dc.identifier.doi | 10.1042/BJ20131025 | - |
dc.date.updated | 2015-06-19T09:30:13Z | - |
dc.description.version | Peer Reviewed | - |
dc.language.rfc3066 | eng | - |
dc.contributor.funder | Ministerio de Ciencia e Innovación (España) | - |
dc.contributor.funder | Junta de Castilla y León | - |
dc.relation.csic | Sí | - |
dc.identifier.funder | http://dx.doi.org/10.13039/501100004837 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100014180 | es_ES |
dc.type.coar | http://purl.org/coar/resource_type/c_6501 | es_ES |
item.openairetype | artículo | - |
item.grantfulltext | none | - |
item.cerifentitytype | Publications | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.fulltext | No Fulltext | - |
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