Abstract
Mitochondria are now recognized as one of the main intracellular calcium-storing organelles which play a key role in the intracellular calcium signalling. Indeed, besides performing oxidative phosphorylation, mitochondria are able to sense and shape calcium (Ca2+) transients, thus controlling cytosolic Ca2+ signals and Ca2+-dependent protein activity. It has been well established for many years that mitochondria have a huge capacity to accumulate calcium. While the physiological significance of this pathway was hotly debated until relatively recently, it is now clear that the ability of mitochondria in calcium handling is a ubiquitous phenomenon described in every cell system in which the issue has been addressed.
In this chapter, we will review the molecular mechanisms involved in the regulation of mitochondrial calcium cycling in physiological conditions with particular regard to the role played by the mitochondrial Na+/Ca2+ exchanger.
An erratum to this chapter can be found at http://dx.doi.org/10.1007/978-1-4614-4756-6_38
An erratum to this chapter can be found at http://dx.doi.org/10.1007/978-1-4614-4756-6_38
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
L. Annunziato, G. Pignataro, G.F. Di Renzo, Pharmacology of brain Na+/Ca2+ exchanger: from molecular biology to therapeutic perspectives. Pharmacol. Rev. 56, 633–654 (2004)
A. Atlante, A. Bobba, P. Calissano, S. Passarella, E. Marra, The apoptosis/necrosis transition in cerebellar granule cells depends on the mutual relationship of the antioxidant and the proteolytic systems which regulate ROS production and cytochrome c release en route to death. J. Neurochem. 84, 960–971 (2003)
D.F. Babcock, J. Herrington, P.C. Goodwin, Y.B. Park, B. Hille, Mitochondrial participation in the intracellular Ca2+ network. J. Cell Biol. 136, 833–844 (1997)
J.M. Baughman, F. Perocchi, H.S. Girgis, M. Plovanich, C.A. Belcher-Timme, Y. Sancak, X.R. Bao, L. Strittmatter, O. Goldberger, R.L. Bogorad, V. Koteliansky, V.K. Mootha, Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter. Nature 476, 341–345 (2011)
P. Bernardi, Mitochondrial transport of cations: channels, exchangers, and permeability transition. Physiol. Rev. 79, 1127–1155 (1999)
C.H. Berthold, C. Fabricius, M. Rydmark, B. Andersen, Axoplasmic organelles at nodes of Ranvier. I. Occurrence and distribution in large myelinated spinal root axons of the adult cat. J. Neurocytol. 22, 925–940 (1993)
E.A. Bristow, P.G. Griffiths, R.M. Andrews, M.A. Johnson, D.M. Turnbull, The distribution of mitochondrial activity in relation to optic nerve structure. Arch. Ophthalmol. 120, 791–796 (2002)
L. Buntinas, K.K. Gunter, G.C. Sparagna, T.E. Gunter, The rapid mode of calcium uptake into heart mitochondria (RaM): comparison to RaM in liver mitochondria. Biochim. Biophys. Acta 1504, 248–261 (2001)
E. Carafoli, Historical review: mitochondria and calcium: ups and downs of an unusual relationship. Trends Biochem. Sci. 28, 175–181 (2003)
E. Carafoli, R. Tiozzo, G. Lugli, F. Crovetti, C. Kratzing, The release of calcium from heart mitochondria by sodium. J. Mol. Cell. Cardiol. 6, 361–371 (1974)
M. Chiesi, R. Schwaller, K. Eichenberger, Structural dependency of the inhibitory action of benzodiazepines and related compounds on the mitochondrial Na+-Ca2+ exchanger. Biochem. Pharmacol. 22, 4399–4403 (1988)
M. Crompton, E. Barksby, N. Johnson, M. Capano, Mitochondrial intermembrane junctional complexes and their involvement in cell death. Biochimie 84, 143–152 (2002)
D.A. Cox, L. Conforti, N. Sperelakis, M.A. Matlib. Selectivity of inhibition of Na(+)-Ca2+ exchange of heart mitochondria by benzothiazepine CGP-37157. J. Cardiovasc. Pharmacol. 21, 595–599 (1993)
D. De Stefani, A. Raffaello, E. Teardo, I. Szabo, R. Rizzuto, A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter. Nature 476, 336–340 (2011)
C. Du, M. Fang, Y. Li, L. Li, X. Wang, Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell 102, 33–42 (2000)
L.L. Dugan, D.W. Choi, Excitotoxicity, free radicals, and cell membrane changes. Ann. Neurol. 35, S17–S21 (1994)
M. Erecinska, I.A. Silver, Ions and energy in mammalian brain. Prog. Neurobiol. 43, 37–71 (1994)
E.J. Harris, Modulation of Ca2+ efflux from heart mitochondria. Biochem. J. 178, 673–680 (1979)
L.S. Jouaville, F. Ichas, E.L. Holmuhamedov, P. Camacho, J.D. Lechleiter, Synchronization of calcium waves by mitochondrial substrates in Xenopus laevis oocytes. Nature 377, 438–441 (1995)
G.H. Kageyama, M.T. Wong-Riley, Histochemical localization of cytochrome oxidase in the hippocampus: correlation with specific neuronal types and afferent pathways. Neuroscience 7, 2337–2361 (1982)
A.L. Lehninger, A. Vercesi, E.A. Bababunmi, Regulation of Ca2+ release from mitochondria by the oxidation-reduction state of pyridine nucleotides. Proc. Natl. Acad. Sci. U. S. A. 75, 1690–1694 (1978)
P. Li, D. Nijhawan, I. Budihardjo, S.M. Srinivasula, M. Ahmad, E.S. Alnemri, X. Wang, Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 91, 479–489 (1997)
A. Livigni, A. Scorziello, S.Agnese, A. Adornetto, A. Carlucci, C. Garbi, I. Castaldo, L. Annunziato, E.V. Avvedimento, A. Feliciello, Mitochondrial AKAP121 links cAMP and src signaling to oxidative metabolism. Mol. Biol. Cell 17, 263–271 (2006)
C. Murgia, P. Giorgi, P. Pinton, R. Rizzuto, Controlling metabolism and cell death: at the heart of mitochondrial calcium signaling. J. Mol. Cell. Cardiol. 46, 781–788 (2009)
D.G. Nicholls, The regulation of extramitochondrial free calcium ion concentration by rat liver mitochondria. Biochem. J. 176, 463–474 (1978)
D.G. Nicholls, Mitochondrial membrane potential and aging. Aging Cell 3, 35–40 (2004)
D.G. Nicholls, M. Crompton, Mitochondrial calcium transport. FEBS Lett. 111, 261–268 (1980)
S.M. Nicolau, Mitochondrial Na+/Ca2+-exchanger blocker CGP37157 protects against chromaffin cell death elicited by veratridine. J. Pharmacol. Exp. Ther. 330(3), 844–854 (2009)
R. Palty, W.F. Silverman, M. Hershfinkel, T. Caporale, S.L. Sensi, J. Parnis, C. Nolte, D. Fishman, V. Shoshan-Barmatz, S. Herrmann, D. Khananshvili, I. Sekler, NCLX is an essential component of mitochondrial Na+/Ca2+ exchange. Proc. Natl. Acad. Sci. U. S. A. 107, 436–441 (2010)
G. Petrosillo, F.M. Ruggiero, M. Pistolese, G. Paradies, Ca2+-induced reactive oxygen species production promotes cytochrome c release from rat liver mitochondria via mitochondrial permeability transition (MPT)-dependent and MPT-independent mechanisms: role of cardiolipin. J. Biol. Chem. 279, 53103–53108 (2004)
C. Ramachandran, F.L. Bygrave, Calcium ion cycling in rat liver mitochondria. Biochem. J. 174, 613–620 (1978)
R. Rizzuto, P. Bernardi, T. Pozzan, Mitochondria as all-round players of the calcium game. J. Physiol. 1, 37–47 (2000)
K.C. Rowland, N.K. Irby, G.A. Spirou, Specialized synapse-associated structures within the calyx of Held. J. Neurosci. 20, 9135–9144 (2000)
N.E. Saris, E. Carafoli, A historical review of cellular calcium handling, with emphasis on mitochondria. Biochemistry (Mosc.) 70, 187–194 (2005)
A. Scorziello, M. Santillo, A. Adornetto, C. Dell’Aversano, R. Sirabella, S. Damiano, L.M. Canzoniero, G.F. Renzo, L. Annunziato, NO-induced neuroprotection in ischemic preconditioning stimulates mitochondrial Mn-SOD activity and expression via Ras/ERK1/2 pathway. J. Neurochem. 103, 1472–80 (2007)
G.C. Sparagna, K.K. Gunter, S.S. Sheu, T.E. Gunter, Mitochondrial calcium uptake from physiological-type pulses of calcium. A description of the rapid uptake mode. J. Biol. Chem. 270, 27510–27515 (1995)
S.A. Susin, H.K. Lorenzo, N. Zamzami, I. Marzo, B.E. Snow, G.M. Brothers, J. Mangion, E. Jacotot, P. Costantini, M. Loeffler, N. Larochette, D.R. Goodlett, R. Aebersold, D.P. Siderovski, J.M. Penninger, G. Kroemer, Molecular characterization of mitochondrial apoptosis-inducing factor. Nature 397, 441–446 (1999)
G. Szabadkai, M.R. Duchen, Mitochondria: the hub of cellular Ca2+ signaling. Physiology (Bethesda) 23, 84–94 (2008)
A.M. Verhagen, P.G. Ekert, M. Pakusch, J. Silke, L.M. Connolly, G.E. Reid, R.L. Moritz, R.J. Simpson, D.L. Vaux, Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins. Cell 102, 43–53 (2000)
J.L. Werth, S.A. Thayer, Mitochondria buffer physiological calcium loads in cultured rat dorsal root ganglion neurons. J. Neurosci. 14, 348–356 (1994)
Acknowledgments
This work was supported by COFIN2008; Ricerca-Sanitaria RF-FSL352059 Ricerca finalizzata 2006; Ricerca-Oncologica 2006; Progetto-Strategico 2007; Progetto Ordinario 2007; Ricerca finalizzata 2009; Ricerca-Sanitaria progetto Ordinario by Ministero della Salute 2008 all to LA
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer Science+Business Media New York
About this chapter
Cite this chapter
Scorziello, A. et al. (2013). New Insights in Mitochondrial Calcium Handling by Sodium/Calcium Exchanger. In: Annunziato, L. (eds) Sodium Calcium Exchange: A Growing Spectrum of Pathophysiological Implications. Advances in Experimental Medicine and Biology, vol 961. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-4756-6_17
Download citation
DOI: https://doi.org/10.1007/978-1-4614-4756-6_17
Published:
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4614-4755-9
Online ISBN: 978-1-4614-4756-6
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)