The DOI matches its Crossref record; 210 of the 215 references it cites were found in a registry or an index.
Molecular nature and regulation of the mitochondrial permeability transition pore(s), drug target(s) in cardioprotection
Abstract
The mitochondrial permeability transition, an established mechanism for heart diseases, is a long-standing mystery of mitochondrial biology and a prime drug target for cardioprotection. Several hypotheses about its molecular nature have been put forward over the years, and the prevailing view is that permeabilization of the inner mitochondrial membrane follows opening of a high-conductance channel, the permeability transition pore, which is also called mitochondrial megachannel or multiconductance channel. The permeability transition strictly requires matrix Ca 2+ and is favored by the matrix protein cyclophilin D, which mediates the inhibitory effects of cyclosporin A. Here we provide a review of the field, with specific emphasis on the possible role of the adenine nucleotide translocator and of the F-ATP synthase in channel formation, and on currently available small molecule inhibitors. While the possible mechanisms through which the adenine nucleotide translocator and the F-ATP synthase might form high-conductance channels remain unknown, reconstitution experiments and site-directed mutagenesis combined to electrophysiology have provided important clues. The hypothesis that more than one protein may act as a permeability transition pore provides a reasonable explanation for current controversies in the field, and holds great promise for the solution of the mystery of the permeability transition.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“The inescapable conclusion from these studies is that some combination of these proteins is necessary to fully exhibit the properties of mPTP [1,18,20,21].”
From The mitochondrial permeability transition: Nexus of aging, disease and longevity (2021) · cites this paper as [1]
Citations
Cites
Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes
Liu, J., Farmer, J. D., Lane, W. S., Friedman, J., Weissman, I., & Schreiber, S. L. (1991) · Cell · doi:10.1016/0092-8674(91)90124-h · Cited by 4,116
Baines, C. P., Kaiser, R. A., Purcell, N. H., Blair, N. S., Osinska, H., Hambleton, M. A., Brunskill, E. W., Sayen, M. R., Gottlieb, R. A., Dorn, G. W., et al. (2005) · Nature · doi:10.1038/nature03434 · Cited by 2,280
Mechanisms by which mitochondria transport calcium
Gunter, T. E., & Pfeiffer, D. R. (1990) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1990.258.5.c755 · Cited by 1,640
Identification of calcineurin as a key signalling enzyme in T-lymphocyte activation
Clipstone, N. A., & Crabtree, G. R. (1992) · Nature · doi:10.1038/357695a0 · Cited by 1,635
Nakagawa, T., Shimizu, S., Watanabe, T., Yamaguchi, O., Otsu, K., Yamagata, H., Inohara, H., Kubo, T., & Tsujimoto, Y. (2005) · Nature · doi:10.1038/nature03317 · Cited by 1,635
The cell biology of mitochondrial membrane dynamics
Giacomello, M., Pyakurel, A., Glytsou, C., & Scorrano, L. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0210-7 · Cited by 1,550
Mechanisms Underlying Acute Protection From Cardiac Ischemia-Reperfusion Injury
Murphy, E., & Steenbergen, C. (2008) · Physiological Reviews · doi:10.1152/physrev.00024.2007 · Cited by 1,504
Effect of Cyclosporine on Reperfusion Injury in Acute Myocardial Infarction
Piot, C. A., Croisille, P., Staat, P., Thibault, H., Rioufol, G., Mewton, N., Belghiti, R. E., Cung, T. T., Bonnefoy‐Cudraz, E., Angoulvant, D., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa071142 · Cited by 1,339
Dephosphorylation by calcineurin regulates translocation of Drp1 to mitochondria
Cereghetti, G. M., Stangherlin, A., de Brito, O. M., Chang, C. R., Blackstone, C., Bernardi, P., & Scorrano, L. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808249105 · Cited by 1,129
Self-citationThe ADP/ATP translocator is not essential for the mitochondrial permeability transition pore
Kokoszka, J. E., Waymire, K. G., Levy, S. E., Sligh, J. E., Cai, J., Jones, D. P., MacGregor, G. R., & Wallace, D. C. (2004) · Nature · doi:10.1038/nature02229 · Cited by 1,086
Research works printed but not linked: 4
- Raaflaub, 1953, Die schwellung isolierter leberzell mitochondrien und ihre physikalisch beeinfluβarkeit, Helv. Physiol. Pharmacol. Acta, 11, 142
- Raaflaub, 1953, Über den wirkungsmechanismus von adenosintriphosphat (ATP) als cofaktor isolierter mitochondrien, Helv. Physiol. Pharmacol. Acta, 11, 157
- Gerle, 1857, On the structural possibility of pore-forming mitochondrial FoF1 ATP synthase, Biochim. Biophys. Acta, 2016, 1191
- Flisiak, 2006, The cyclophilin inhibitor Debio-025 Has a Potent Dual Anti-Hiv and Anti-Hcv Activity in treatment-Naive Hiv/Hcv Co-infected subjects, Hepatology, 44
Cited by
Sorted by citations
Bernardi, P., Gerle, C., Halestrap, A. P., Jonas, E. A., Karch, J. M., Mnatsakanyan, N., Pavlov, E. V., Sheu, S., & Soukas, A. A. (2023) · Cell Death and Differentiation · doi:10.1038/s41418-023-01187-0 · Cited by 504
Self-citationMitochondrial pores at the crossroad between cell death and inflammatory signaling
Flores‐Romero, H., Dadsena, S., & García‐Sáez, A. J. (2023) · Molecular Cell · doi:10.1016/j.molcel.2023.02.021 · Cited by 131
Manolis, A. S., Manolis, A. A., Manolis, T. A., Apostolaki, N. E., Apostolopoulos, E. J., Melita, H., & Katsiki, N. (2020) · Medicinal Research Reviews · doi:10.1002/med.21732 · Cited by 116
Ca2+ handling at the mitochondria-ER contact sites in neurodegeneration
Lim, D., Dematteis, G., Tapella, L., Genazzani, A. A., Calí, T., Brini, M., & Verkhratsky, A. (2021) · Cell Calcium · doi:10.1016/j.ceca.2021.102453 · Cited by 109
The mitochondrial permeability transition: Nexus of aging, disease and longevity
Rottenberg, H., & Hoek, J. B. (2021) · Cells · doi:10.3390/cells10010079 · Cited by 94
“5 nS) that is activated by calcium, oxidative stress and membrane depolarization [1,2].”
BackgroundInfluential
Metadata
- Authors
- Carraro, M., Carrer, A., Urbani, A., & Bernardi, P.
- Affiliations
- University of Padua (IT)
- Corresponding author
- Bernardi, Paolo
- Venue
- Journal of Molecular and Cellular Cardiology
- Publisher
- Elsevier BV
- Published
- 2020-07
- Volume
- 144
- Pages
- 76-86
- ISSN
- 0022-2828 (ISSN-L)
- OpenAlex
- W3028471616
- Cited by
- 71
- References
- 215
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 3 · 2023: 8 · 2022: 11 · 2021: 20 · 2020: 15
- FWCI
- 4.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Molecular and Cellular Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Funders
- Fondazione Telethon
- Ministero dell’Istruzione, dell’Università e della Ricerca
- Fondation Leducq
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Ischemia and Reperfusion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
- Keywords
- mitochondrial permeability transition, mitochondrial permeability transition pore, cardioprotection, cyclophilin D, cyclosporine, adenine nucleotide translocase, F-ATP synthase, mitochondrial matrix calcium, small molecule inhibitors, heart disease
- MeSH terms
- Mitochondrial Permeability Transition Pore, Animals, Cardiotonic Agents, Mitochondria, Heart, Permeability, Protein Binding, Biomarkers, Mice, Knockout, Mitochondrial Proton-Translocating ATPases, Organic Anion Transporters, Mice, Protein Interaction Domains and Motifs, Protein Multimerization, Drug Discovery
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
