The permeability transition pore as a Ca(2+) release channel: new answers to an old question
- PMID: 22513364
- PMCID: PMC3396848
- DOI: 10.1016/j.ceca.2012.03.004
The permeability transition pore as a Ca(2+) release channel: new answers to an old question
Abstract
Mitochondria possess a sophisticated array of Ca(2+) transport systems reflecting their key role in physiological Ca(2+) homeostasis. With the exception of most yeast strains, energized organelles are endowed with a very fast and efficient mechanism for Ca(2+) uptake, the ruthenium red (RR)-sensitive mitochondrial Ca(2+) uniporter (MCU); and one main mechanism for Ca(2+) release, the RR-insensitive 3Na(+)-Ca(2+) antiporter. An additional mechanism for Ca(2+) release is provided by a Na(+) and RR-insensitive release mechanism, the putative 3H(+)-Ca(2+) antiporter. A potential kinetic imbalance is present, however, because the V(max) of the MCU is of the order of 1400nmol Ca(2+)mg(-1) proteinmin(-1) while the combined V(max) of the efflux pathways is about 20nmol Ca(2+)mg(-1) proteinmin(-1). This arrangement exposes mitochondria to the hazards of Ca(2+) overload when the rate of Ca(2+) uptake exceeds that of the combined efflux pathways, e.g. for sharp increases of cytosolic [Ca(2+)]. In this short review we discuss the hypothesis that transient opening of the Ca(2+)-dependent permeability transition pore may provide mitocondria with a fast Ca(2+) release channel preventing Ca(2+) overload. We also address the relevance of a mitochondrial Ca(2+) release channel recently discovered in Drosophila melanogaster, which possesses intermediate features between the permeability transition pore of yeast and mammals.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Similar articles
-
Properties of Ca(2+) transport in mitochondria of Drosophila melanogaster.J Biol Chem. 2011 Dec 2;286(48):41163-41170. doi: 10.1074/jbc.M111.268375. Epub 2011 Oct 7. J Biol Chem. 2011. PMID: 21984833 Free PMC article.
-
Deletion of mitochondrial calcium uniporter incompletely inhibits calcium uptake and induction of the permeability transition pore in brain mitochondria.J Biol Chem. 2018 Oct 5;293(40):15652-15663. doi: 10.1074/jbc.RA118.002926. Epub 2018 Aug 28. J Biol Chem. 2018. PMID: 30154242 Free PMC article.
-
Mitochondrial Ca2+ influx and efflux rates in guinea pig cardiac mitochondria: low and high affinity effects of cyclosporine A.Biochim Biophys Acta. 2011 Jul;1813(7):1373-81. doi: 10.1016/j.bbamcr.2011.02.012. Epub 2011 Feb 26. Biochim Biophys Acta. 2011. PMID: 21362444 Free PMC article.
-
Measurement of mitochondrial Ca2+ transport mediated by three transport proteins: VDAC1, the Na+/Ca2+ exchanger, and the Ca2+ uniporter.Cold Spring Harb Protoc. 2014 Feb 1;2014(2):161-6. doi: 10.1101/pdb.top066241. Cold Spring Harb Protoc. 2014. PMID: 24492769 Review.
-
Glutamate excitotoxicity and Ca2+-regulation of respiration: Role of the Ca2+ activated mitochondrial transporters (CaMCs).Biochim Biophys Acta. 2016 Aug;1857(8):1158-1166. doi: 10.1016/j.bbabio.2016.04.003. Epub 2016 Apr 7. Biochim Biophys Acta. 2016. PMID: 27060251 Review.
Cited by
-
Mechanism and treatment of intracerebral hemorrhage focus on mitochondrial permeability transition pore.Front Mol Neurosci. 2024 Jul 31;17:1423132. doi: 10.3389/fnmol.2024.1423132. eCollection 2024. Front Mol Neurosci. 2024. PMID: 39156127 Free PMC article. Review.
-
Extracellular freezing induces a permeability transition in the inner membrane of muscle mitochondria of freeze-sensitive but not freeze-tolerant Chymomyza costata larvae.Front Physiol. 2024 Feb 7;15:1358190. doi: 10.3389/fphys.2024.1358190. eCollection 2024. Front Physiol. 2024. PMID: 38384799 Free PMC article.
-
Signaling Roleplay between Ion Channels during Mammalian Sperm Capacitation.Biomedicines. 2023 Sep 12;11(9):2519. doi: 10.3390/biomedicines11092519. Biomedicines. 2023. PMID: 37760960 Free PMC article. Review.
-
Identity, structure, and function of the mitochondrial permeability transition pore: controversies, consensus, recent advances, and future directions.Cell Death Differ. 2023 Aug;30(8):1869-1885. doi: 10.1038/s41418-023-01187-0. Epub 2023 Jul 17. Cell Death Differ. 2023. PMID: 37460667 Free PMC article. Review.
-
Long-term potentiation and spatial memory training stimulate the hippocampal expression of RyR2 calcium release channels.Front Cell Neurosci. 2023 Mar 21;17:1132121. doi: 10.3389/fncel.2023.1132121. eCollection 2023. Front Cell Neurosci. 2023. PMID: 37025696 Free PMC article.
References
-
- Scarpa A., Azzone G.F. The mechanism of ion translocation in mitochondria. 4. Coupling of K+ efflux with Ca2+ uptake. Eur. J. Biochem. 1970;12:328–335. - PubMed
-
- Wingrove D.E., Amatruda J.M., Gunter T.E. Glucagon effects on the membrane potential and calcium uptake rate of rat liver mitochondria. J. Biol. Chem. 1984;259:9390–9394. - PubMed
-
- Kirichok Y., Krapivinsky G., Clapham D.E. The mitochondrial calcium uniporter is a highly selective ion channel. Nature. 2004;427:360–364. - PubMed
-
- Baughman J.M., Perocchi F., Girgis H.S., Plovanich M., Belcher-Timme C.A., Sancak Y., Bao X.R., Strittmatter L., Goldberger O., Bogorad R.L., Koteliansky V., Mootha V.K. Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter. Nature. 2011;476:341–345. - PMC - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
Miscellaneous