PLoS ONE (Jan 2016)

By Regulating Mitochondrial Ca2+-Uptake UCP2 Modulates Intracellular Ca2+.

  • Lukas Jaroslaw Motloch,
  • Robert Larbig,
  • Tina Gebing,
  • Sara Reda,
  • Astrid Schwaiger,
  • Johannes Leitner,
  • Martin Wolny,
  • Lars Eckardt,
  • Uta C Hoppe

DOI
https://doi.org/10.1371/journal.pone.0148359
Journal volume & issue
Vol. 11, no. 2
p. e0148359

Abstract

Read online

The possible role of UCP2 in modulating mitochondrial Ca2+-uptake (mCa2+-uptake) via the mitochondrial calcium uniporter (MCU) is highly controversial.Thus, we analyzed mCa2+-uptake in isolated cardiac mitochondria, MCU single-channel activity in cardiac mitoplasts, dual Ca2+-transients from mitochondrial ((Ca2+)m) and intracellular compartment ((Ca2+)c) in the whole-cell configuration in cardiomyocytes of wild-type (WT) and UCP2-/- mice.Isolated mitochondria showed a Ru360 sensitive mCa2+-uptake, which was significantly decreased in UCP2-/- (229.4±30.8 FU vs. 146.3±23.4 FU, P0.05) and transsarcolemmal Ca2+-influx was inhibited suggesting a possible compensatory mechanism. Additionally, we observed an inhibitory effect of ATP on mCa2+-uptake in WT mitoplasts and (Ca2+)m of cardiomyocytes leading to an increase of (Ca2+)c while no ATP dependent effect was observed in UCP2-/-.Our results indicate regulatory effects of UCP2 on mCa2+-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.