Journal
CELL CALCIUM
Volume 48, Issue 5, Pages 288-301Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.ceca.2010.10.004
Keywords
Ca2+ signaling; Ca2+ release; Store-operated Ca2+ entry; Endothelial cells; Mitochondrial Ca2+ signaling; Mitochondrial Ca2+ uniport
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Funding
- Austrian Science Funds [P20181-B5, P21857-B18, F3010-B05]
- Austrian Ministry of Education, Science and Culture
- Austrian Science Fund (FWF) [P 21857] Funding Source: researchfish
- Austrian Science Fund (FWF) [P21857, P20181] Funding Source: Austrian Science Fund (FWF)
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Uncoupling proteins 2 and 3 (UCP2/3) are essential for mitochondrial Ca2+ uptake but both proteins exhibit distinct activities in regard to the source and mode of Ca2+ mobilization. In the present work, structural determinants of their contribution to mitochondrial Ca2+ uptake were explored. Previous findings indicate the importance of the intermembrane loop 2 (IML2) for the contribution of UCP2/3. Thus, the IML2 of UCP2/3 was substituted by that of UCP1. These chimeras had no activity in mitochondrial uptake of intracellularly released Ca2+, while they mimicked the wild-type proteins by potentiating mitochondrial sequestration of entering Ca2+. Alignment of the IML2 sequences revealed that UCP1, UCP2 and UCP3 share a basic amino acid in positions 163, 164 and 167, while only UCP2 and UCP3 contain a second basic residue in positions 168 and 171, respectively. Accordingly, mutants of UCP3 in positions 167 and 171/172 were made. In permeabilized cells, these mutants exhibited distinct Ca2+ sensitivities in regard to mitochondrial Ca2+ sequestration. In intact cells, these mutants established different activities in mitochondrial uptake of either intracellularly released (UCP3(R171,E172)) or entering (UCP3(R167)) Ca2+. Our data demonstrate that distinct sites in the IML2 of UCP3 effect mitochondrial uptake of high and low Ca2+ signals. (C) 2010 Elsevier Ltd. All rights reserved.
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