RT info:eu-repo/semantics/article
T1 Dynamics of mitochondrial Ca2+ uptake in MICU1-knockdown cells
A1 de la Fuente, Sergio
A1 Matesanz-Isabel, Jessica
A1 Fonteriz, Rosalba I.
A1 Montero, Mayte
A1 Alvarez, Javier
AB 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.
PB portland press
SN 0264-6021
YR 2014
FD 2014-02-15
LK https://uvadoc.uva.es/handle/10324/67171
UL https://uvadoc.uva.es/handle/10324/67171
LA eng
NO de la Fuente S, Matesanz-Isabel J, Fonteriz RI, Montero M, Alvarez J. Dynamics of mitochondrial Ca2+ uptake in MICU1-knockdown cells. Biochem J. 2014 Feb 15;458(1):33-40. doi: 10.1042/BJ20131025. PMID: 24313810.
NO Producción Científica
DS UVaDOC
RD 28-nov-2024