Open AccessBy Regulating Mitochondrial Ca2+-Uptake UCP2 Modulates Intracellular Ca2+
Author(s) -
Lukas J. Motloch,
Robert Larbig,
Tina Gebing,
Sara Reda,
Astrid Schwaiger,
Johannes Leitner,
Martin Wolny,
Lars Eckardt,
Uta C. Hoppe
Publication year - 2016
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0148359
Subject(s) - intracellular , mitochondrion , chemistry , microbiology and biotechnology , biophysics , biology
The possible role of UCP2 in modulating mitochondrial Ca 2+ -uptake (mCa 2+ -uptake) via the mitochondrial calcium uniporter (MCU) is highly controversial. Methods Thus, we analyzed mCa 2+ -uptake in isolated cardiac mitochondria, MCU single-channel activity in cardiac mitoplasts, dual Ca 2+ -transients from mitochondrial ((Ca 2+ )m) and intracellular compartment ((Ca 2+ )c) in the whole-cell configuration in cardiomyocytes of wild-type (WT) and UCP2 -/- mice. Results Isolated mitochondria showed a Ru360 sensitive mCa 2+ -uptake, which was significantly decreased in UCP2 -/- (229.4±30.8 FU vs. 146.3±23.4 FU, P<0 . 05 ). Single-channel registrations confirmed a Ru360 sensitive voltage-gated Ca 2+ -channel in mitoplasts, i.e. mCa1, showing a reduced single-channel activity in UCP2 -/- (Po,total: 0.34±0.05% vs. 0.07±0.01%, P <0.05). In UCP2 -/- cardiomyocytes (Ca 2+ )m was decreased (0.050±0.009 FU vs. 0.021±0.005 FU, P<0 . 05 ) while (Ca 2+ )c was unchanged (0.032±0.002 FU vs. 0.028±0.004 FU, P>0 . 05 ) and transsarcolemmal Ca 2+ -influx was inhibited suggesting a possible compensatory mechanism. Additionally, we observed an inhibitory effect of ATP on mCa 2+ -uptake in WT mitoplasts and (Ca 2+ )m of cardiomyocytes leading to an increase of (Ca 2+ )c while no ATP dependent effect was observed in UCP2 -/- . Conclusion Our results indicate regulatory effects of UCP2 on mCa 2+ -uptake. Furthermore, we propose, that previously described inhibitory effects on MCU by ATP may be mediated via UCP2 resulting in changes of excitation contraction coupling.