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SHR Neuro Cancer Cardio Lipid Metab Microb
Bondarenko, AI; Parichatikanond, W; Madreiter, CT; Rost, R; Waldeck-Weiermair, M; Malli, R; Graier, WF.
UCP2 modulates single-channel properties of a MCU-dependent Ca(2+) inward current in mitochondria.
Pflugers Arch. 2015; 467(12):2509-2518
Doi: 10.1007/s00424-015-1727-z
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- Leading authors Med Uni Graz
- Bondarenko Oleksandr
- Graier Wolfgang
- Co-authors Med Uni Graz
- Madreiter-Sokolowski Corina
- Malli Roland
- Parichatikanond Warisara
- Rost René
- Waldeck-Weiermair Markus
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- Abstract:
- The mitochondrial Ca(2+) uniporter is a highly Ca(2+)-selective protein complex that consists of the pore-forming mitochondrial Ca(2+) uniporter protein (MCU), the scaffolding essential MCU regulator (EMRE), and mitochondrial calcium uptake 1 and 2 (MICU1/2), which negatively regulate mitochondrial Ca(2+) uptake. We have previously reported that uncoupling proteins 2 and 3 (UCP2/3) are also engaged in the activity of mitochondrial Ca(2+) uptake under certain conditions, while the mechanism by which UCP2/3 facilitates mitochondrial Ca(2+) uniport remains elusive. This work was designed to investigate the impact of UCP2 on the three distinct mitochondrial Ca(2+) currents found in mitoplasts isolated from HeLa cells, the intermediate- (i-), burst- (b-) and extra-large (xl-) mitochondrial/mitoplast Ca(2+) currents (MCC). Using the patch clamp technique on mitoplasts from cells with reduced MCU and EMRE unveiled a very high affinity of MCU for xl-MCC that succeeds that for i-MCC, indicating the coexistence of at least two MCU/EMRE-dependent Ca(2+) currents. The manipulation of the expression level of UCP2 by either siRNA-mediated knockdown or overexpression changed exclusively the open probability (NPo) of xl-MCC by approx. 38% decrease or nearly a 3-fold increase, respectively. These findings confirm a regulatory role of UCP2 in mitochondrial Ca(2+) uptake and identify UCP2 as a selective modulator of just one distinct MCU/EMRE-dependent mitochondrial Ca(2+) inward current.
- Find related publications in this database (using NLM MeSH Indexing)
- Calcium - metabolism
- Calcium Channels - metabolism
- HeLa Cells -
- Humans -
- Ion Channels - genetics
- Ion Channels - metabolism
- Membrane Potential, Mitochondrial -
- Mitochondria - metabolism
- Mitochondria - physiology
- Mitochondrial Proteins - genetics
- Mitochondrial Proteins - metabolism
- Uncoupling Protein 2 -
- Find related publications in this database (Keywords)
- Mitochondrial Ca2+ channels
- Mitochondrial Ca2+ currents
- Mitochondrial Ca2+ uniporter
- Mitoplast
- Uncoupling protein 2
- Patch clamp