Abstract
The mitochondrial Ca2+ uniporter is a highly Ca2+-selective protein complex that consists of the pore-forming mitochondrial Ca2+ uniporter protein (MCU), the scaffolding essential MCU regulator (EMRE), and mitochondrial calcium uptake 1 and 2 (MICU1/2), which negatively regulate mitochondrial Ca2+ uptake. We have previously reported that uncoupling proteins 2 and 3 (UCP2/3) are also engaged in the activity of mitochondrial Ca2+ uptake under certain conditions, while the mechanism by which UCP2/3 facilitates mitochondrial Ca2+ uniport remains elusive. This work was designed to investigate the impact of UCP2 on the three distinct mitochondrial Ca2+ currents found in mitoplasts isolated from HeLa cells, the intermediate- (i-), burst- (b-) and extra-large (xl-) mitochondrial/mitoplast Ca2+ 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 Ca2+ 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 Ca2+ uptake and identify UCP2 as a selective modulator of just one distinct MCU/EMRE-dependent mitochondrial Ca2+ inward current.
Highlights
IntroductionGreat progress in the molecular identification of the proteins responsible for mitochondrial Ca2+ uptake has been achieved recently
After decades of research, great progress in the molecular identification of the proteins responsible for mitochondrial Ca2+ uptake has been achieved recently
We have previously described that uncoupling proteins 2 and 3 (UCP2/3) are fundamentally involved in the activity of mitochondrial Ca2+ uptake under certain conditions [36]
Summary
Great progress in the molecular identification of the proteins responsible for mitochondrial Ca2+ uptake has been achieved recently. Following the landmark discovery of mitochondrial calcium uptake 1 (MICU1) by the group of Vamsi K. Mootha in the year 2010 [27], further components of the protein complex that achieves mitochondrial Ca2+ sequestration have been identified: the mitochondrial Ca2+ uniporter (MCU) [1, 10], MICU1, MICU2, and MICU3 [28], and the essential MCU regulator (EMRE) [32]. Our data on the role of UCP2/3 in mitochondrial Ca2+ uptake indicate a regulatory function of UCP2/3 on MCU-dependent mitochondrial Ca2+ uniporter under certain conditions while a direct involvement of UCP2/3 as part of the actual Ca2+ pore appears unlikely [15, 35]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
