Springer Berlin Heidelberg
Berlin/Heidelberg
Springer
424
10.1007/424.1432-2013
0031-6768
1432-2013
Pflügers Archiv - European Journal of Physiology
European Journal of Physiology
Pflugers Arch - Eur J Physiol
Biomedicine
Human Physiology
Molecular Medicine
Neurosciences
Cell Biology
Receptors
Biomedical and Life Sciences
470
470
12
8
8
Special Focus on: Mitochondrial Signalling
11
2018
7
13
2018
7
13
2018
8
2018
Springer-Verlag GmbH Germany, part of Springer Nature
2018
Ole
Petersen
Alexei
Tepikin
2123
10.1007/s00424-018-2123-2
4
Mitochondrial calcium uptake in organ physiology: from molecular mechanism to animal models
Invited Review
1165
1179
2018
2
15
2017
10
16
2018
1
16
2018
2
14
2018
3
15
Fondazione Telethon
GGP16029
GGP16026
AFM-Téléthon
18857
19471
Associazione Italiana per la Ricerca sul Cancro
18633
National Institutes of Health
Ministero dell’Istruzione, dell’Università e della Ricerca
The Author(s)
2018
Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Cristina
Mammucari
+390498276481
cristina.mammucari@unipd.it
Anna
Raffaello
Denis
Vecellio Reane
Gaia
Gherardi
Agnese
De Mario
Rosario
Rizzuto
+390498273001
rosario.rizzuto@unipd.it
0000 0004 1757 3470
grid.5608.b
Department of Biomedical Sciences
University of Padova
Padua
Italy
Abstract
Mitochondrial Ca2+ is involved in heterogeneous functions, ranging from the control of metabolism and ATP production to the regulation of cell death. In addition, mitochondrial Ca2+ uptake contributes to cytosolic [Ca2+] shaping thus impinging on specific Ca2+-dependent events. Mitochondrial Ca2+ concentration is controlled by influx and efflux pathways: the former controlled by the activity of the mitochondrial Ca2+ uniporter (MCU), the latter by the Na+/Ca2+ exchanger (NCLX) and the H+/Ca2+ (mHCX) exchanger. The molecular identities of MCU and of NCLX have been recently unraveled, thus allowing genetic studies on their physiopathological relevance. After a general framework on the significance of mitochondrial Ca2+ uptake, this review discusses the structure of the MCU complex and the regulation of its activity, the importance of mitochondrial Ca2+ signaling in different physiological settings, and the consequences of MCU modulation on organ physiology.
Keywords
Mitochondria Ca2+ uptake
Animal models
Heart
Skeletal muscle
Neurons
Pancreatic β cells
This article is part of the special issue on Mitochondrial Signalling in Pflügers Archiv – European Journal of Physiology