The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index.
Bax and Bak function as the outer membrane component of the mitochondrial permeability pore in regulating necrotic cell death in mice
Open accessAbstract
A critical event in ischemia-based cell death is the opening of the mitochondrial permeability transition pore (MPTP). However, the molecular identity of the components of the MPTP remains unknown. Here, we determined that the Bcl-2 family members Bax and Bak, which are central regulators of apoptotic cell death, are also required for mitochondrial pore-dependent necrotic cell death by facilitating outer membrane permeability of the MPTP. Loss of Bax/Bak reduced outer mitochondrial membrane permeability and conductance without altering inner membrane MPTP function, resulting in resistance to mitochondrial calcium overload and necrotic cell death. Reconstitution with mutants of Bax that cannot oligomerize and form apoptotic pores, but still enhance outer membrane permeability, permitted MPTP-dependent mitochondrial swelling and restored necrotic cell death. Our data predict that the MPTP is an inner membrane regulated process, although in the absence of Bax/Bak the outer membrane resists swelling and prevents organelle rupture to prevent cell death.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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
“These include: (1) pro- and anti-apoptotic BCL2 family members such as BAX, BAK, and BID [407–410], as well as BCL2 and BCL-XL [411–414]”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [407]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Danial, N. N., & Korsmeyer, S. J. (2004) · Cell · doi:10.1016/s0092-8674(04)00046-7 · Cited by 4,651
Proapoptotic BAX and BAK: A Requisite Gateway to Mitochondrial Dysfunction and Death
Wei, M. C., Zong, W.-X., Cheng, E. H.-Y., Lindsten, T., Panoutsakopoulou, V., Ross, A. J., Roth, K. A., MacGregor, G. R., Thompson, C. B., & Korsmeyer, S. J. (2001) · Science · doi:10.1126/science.1059108 · Cited by 3,988 · cited 2×
“As previously reported, Bax/Bak1 double-knockout (DKO) MEFs were highly resistant to cell death by the apoptotic inducer staurosporine (Wei et al., 2001), while Wt MEFs showed high levels of killing (Figure 1A).”
BackgroundSelf-citationChemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury
Degterev, A., Huang, Z., Boyce, M., Li, Y., Jagtap, P., Mizushima, N., Cuny, G. D., Mitchison, T. J., Moskowitz, M. A., & Yuan, J. (2005) · Nature Chemical Biology · doi:10.1038/nchembio711 · Cited by 3,068 · cited 2×
“Necroptosis is induced in cells when stimulated with tumor necrosis factor α (TNFα) in the presence of caspase inhibitors, such as zVAD-fmk (Degterev et al., 2005).”
BackgroundMixed Lineage Kinase Domain-like Protein Mediates Necrosis Signaling Downstream of RIP3 Kinase
Sun, L., Wang, H., Wang, Z., He, S., Chen, S., Liao, D., Wang, L., Yan, J., Liu, W., Lei, X., et al. (2012) · Cell · doi:10.1016/j.cell.2011.11.031 · Cited by 2,698 · cited 1×
“Recently, mixed lineage kinase domain–like protein (MLKL) and phosphoglycerate mutase family member 5 (PGAM5) were shown to be downstream of the RIP proteins (Sun et al., 2012; Wang et al., 2012).”
BackgroundMitochondria and cell death: outer membrane permeabilization and beyond
Tait, S. W. G., & Green, D. R. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2952 · Cited by 2,593
Cho, Y., Challa, S., Moquin, D., Genga, R., Ray, T. D., Guildford, M., & Chan, F. K.-M. (2009) · Cell · doi:10.1016/j.cell.2009.05.037 · Cited by 2,435 · cited 1×
“RIP1 is able to interact with RIP3 in controlling necroptosis (Cho et al., 2009; He et al., 2009; Zhang et al., 2009).”
BackgroundBaines, 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 · cited 2×
“Indeed, deletion of the gene encoding CypD renders mitochondria resistant to Ca2+ overload– induced swelling and the heart and brain partially resistant to cell death due to ischemic injury (Baines et al., 2005; Nakagawa et al., 2005; Schinzel et al., 2005).”
BackgroundSelf-citationReceptor Interacting Protein Kinase-3 Determines Cellular Necrotic Response to TNF-α
He, S., Wang, L., Miao, L., Wang, T., Du, F., Zhao, L., & Wang, X. (2009) · Cell · doi:10.1016/j.cell.2009.05.021 · Cited by 2,214 · cited 1×
“RIP1 is able to interact with RIP3 in controlling necroptosis (Cho et al., 2009; He et al., 2009; Zhang et al., 2009).”
BackgroundShimizu, S., Narita, M., Tsujimoto, Y., & Tsujimoto, Y. (1999) · Nature · doi:10.1038/20959 · Cited by 2,178 · cited 1×
“Over a decade ago, several reports suggested that Bax and/or Bak directly interacted with presumed components of the MPTP, the adenine nucleotide translocator (ANT) in the inner membrane and the VDAC in the outer membrane (Marzo et al., 1998; Narita et al., 1998; Shimizu et al., 1999).”
BackgroundRIP3, an Energy Metabolism Regulator That Switches TNF-Induced Cell Death from Apoptosis to Necrosis
Zhang, D.-W., Shao, J., Lin, J., Zhang, N., Lu, B.-J., Lin, S.-C., Dong, M.-Q., & Han, J. (2009) · Science · doi:10.1126/science.1172308 · Cited by 1,931 · cited 1×
“RIP1 is able to interact with RIP3 in controlling necroptosis (Cho et al., 2009; He et al., 2009; Zhang et al., 2009).”
Background
Flagged first, then by citations
Cited by
Sorted by citations
Items 101–200 of 291
PRC2 loss induces chemoresistance by repressing apoptosis in T cell acute lymphoblastic leukemia
Ariës, I. M., Bodaar, K., Karim, S., Chonghaile, T. N., Hinze, L., Burns, M., Pfirrmann, M., Degar, J., Landrigan, J., Balbach, S. T., et al. (2018) · The Journal of Experimental Medicine · doi:10.1084/jem.20180570 · Cited by 60
“…and BCL2-regulated mitochondrial apoptosis are distinct cell death pathways (Baines et al., 2005; Nakagawa et al., 2005; Galluzzi et al., 2015), these do share some cellular machinery (Karch et al., 2013), and it will be of interest to define precisely how TRAP1 regulates mitochondrial apoptosis.”
BackgroundThe Beneficial Roles of SIRT1 in Drug-Induced Liver Injury
Yan, T., Huang, J., Nisar, M. F., Wan, C. C., & Huang, W. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/8506195 · Cited by 60
“The induction of mitochondrial permeability transition (MPT) enhances permeability in the mitochondrial membranes and allows the exit of molecules of variable sizes [44].”
Guo, Q., Kawahata, K., Cheng, A., Wang, H., Jia, W., Yoshino, H., & Fukunaga, K. (2022) · Redox Biology · doi:10.1016/j.redox.2022.102547 · Cited by 58
“and Bcl-2 have a major impact on ischemic neuronal death [33,34].”
BackgroundLi, P., Dong, X., Zhang, B., Zhang, X., Liu, J.-Z., Ma, D., & Ma, L. (2021) · Chinese Medical Journal · doi:10.1097/cm9.0000000000001772 · Cited by 56
“MLKL can destroy the complete structure of cell and organelle membranes, alter cell permeability, and induce necrosis.([17])”
BackgroundBax Regulates Neuronal Ca2+Homeostasis
D’Orsi, B., Kilbride, S. M., Chen, G., Perez‐Alvarez, S., Bonner, H. P., Pfeiffer, S., Plesnila, N., Engel, T., Henshall, D. C., Düßmann, H., et al. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.2453-14.2015 · Cited by 59
“…suggested to regulate Ca 2 homeostasis in non-neuronal cells (Scorrano et al., 2003, Chen et al., 2004b, Mathai et al., 2005, Oakes et al., 2005, Karch et al., 2013), we hypothesized that bax gene deletion may regulate neuronal Ca 2 dynamics, which could explain the broader…”
BackgroundThe Role of BCL-2 Family Members in Acute Kidney Injury
Borkan, S. C. (2016) · Seminars in Nephrology · doi:10.1016/j.semnephrol.2016.04.001 · Cited by 55
Yan, S., Wu, L., Wu, L., Zhong, C., Zhong, C., Yu, Q., Wang, Y., Lue, L., Douglas, J. T., Douglas, J. T., et al. (2016) · Diabetes · doi:10.2337/db16-0556 · Cited by 55
“Mitochondrial Patch Clamp Mitochondrial single-channel patch clamp was performed, as previously described (37,38), with modifications.”
BackgroundMethodLiu, C., Yang, F., Cheng, S., Liu, Y., Wan, L., & Cong, H. (2017) · Cardiovascular Therapeutics · doi:10.1111/1755-5922.12225 · Cited by 52
Tian, M., Xie, Y., Meng, Y., Ma, W., Tong, Z., Yang, X., Lai, S., Zhou, Y., He, M., & Liao, Z. (2019) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2018.11.016 · Cited by 53
Cui, Y., Pan, M., Ma, J., Song, X., Cao, W., & Zhang, P. (2020) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-020-03926-0 · Cited by 52
P38α MAPK underlies muscular dystrophy and myofiber death through a Bax-dependent mechanism
Wissing, E. R., Boyer, J. G., Kwong, J. Q., Sargent, M. A., Karch, J. M., McNally, E. M., Otsu, K., & Molkentin, J. D. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu270 · Cited by 53
Self-citationRegulation of Cell Death by Mitochondrial Transport Systems of Calcium and Bcl-2 Proteins
Naumova, N., & Šachl, R. (2020) · Membranes · doi:10.3390/membranes10100299 · Cited by 53
Solesio, M. E., Elustondo, P. A., Zakharian, E., & Pavlov, E. V. (2016) · Biochemical Society Transactions · doi:10.1042/bst20150206 · Cited by 53
Wang, L., Li, J., Shi, X., Li, S., Tang, P. M., Li, Z., Li, H., & Wei, C. (2018) · Phytomedicine · doi:10.1016/j.phymed.2018.09.221 · Cited by 52
Role of Mitofusins and Mitophagy in Life or Death Decisions
Joaquim, M., & Escobar‐Henriques, M. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.572182 · Cited by 50
Reduced risk of apoptosis: mechanisms of stress responses
Milisav, I., Poljšak, B., & Ribarič, S. (2016) · APOPTOSIS · doi:10.1007/s10495-016-1317-3 · Cited by 49
“Oligomerized BAK and BAX cause mitochondrial outer membrane permeabilization (MOMP) and contribute to mitochondrial permeability transition pore (MPTP) [35].”
BackgroundPromising Strategy of mPTP Modulation in Cancer Therapy: An Emerging Progress and Future Insight
Waseem, M., & Wang, B. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24065564 · Cited by 50
“OMM, outer mitochondrial membrane; IMM, inner mitochondrial membrane; VDAC, voltage‐dependent anion channel (mitochondrial porin); HK‐II, hexokinase II; TSPO, translocator protein; ANT, ade‐ nine nucleotide transporter; CypD, cyclophilin D; Bcl‐2, antiapoptotic protein; BAX, proapoptotic protein.”
BackgroundInfluentialPatel, P., Mendoza, A., Robichaux, D. J., Wang, M. C., Wehrens, X. H. T., & Karch, J. M. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.765973 · Cited by 47
Self-citationWang, W., Fernández‐Sanz, C., & Sheu, S. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2017.09.004 · Cited by 46
“The outer membrane permeabilization is thought to be the first step of mPTP opening [99].”
BackgroundFunctional Role of microRNAs in Regulating Cardiomyocyte Death
Kansakar, U., Varzideh, F., Mone, P., Jankauskas, S. S., & Santulli, G. (2022) · Cells · doi:10.3390/cells11060983 · Cited by 46
“On the other hand, the intrinsic pathway is mainly mediated by mitochondriaassociated BCL-2 family proteins, namely BAX and BAK [37–42], located in the outer mitochondrial membrane [43].”
BackgroundTong, Z., Xie, Y., He, M. L., Ma, W., Zhou, Y., Lai, S., Meng, Y., & Liao, Z. (2017) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2017.08.046 · Cited by 43
“Members of Bcl-2 family control the integrity of the OMM and are crucial in determining the susceptibility of cells to apoptosis induced by the mitochondria-mediated pathway [20].”
BackgroundMyocardin regulates mitochondrial calcium homeostasis and prevents permeability transition
Mughal, W., Martens, M. D., Field, J. T., Chapman, D. C., Huang, J., Rattan, S. G., Hai, Y., Cheung, K. G., Kereliuk, S. M., West, A. R., et al. (2018) · Cell Death and Differentiation · doi:10.1038/s41418-018-0073-z · Cited by 43
“serve as outer member modulators of permeability transition [16].”
BackgroundRuiz, A., Quintela‐López, T., Sánchez‐Gómez, M. V., Gaminde‐Blasco, A., Alberdi, E. M., & Matute, C. (2020) · Glia · doi:10.1002/glia.23802 · Cited by 43
“Indeed, mitochondrial swelling caused by mitochondrial per- meability transition pore opening is a hallmark of necrotic cell death (Karch et al., 2013), a major cell death mechanism contributing to oli- godendroglial excitotoxicity (Leuchtmann, Ratner, Vijitruth, Qu, & McDonald, 2003).”
BackgroundPekson, R., Liang, F. G., Axelrod, J. L., Lee, J., Qin, D., Wittig, A. J. H., Paulino, V. M., Zheng, M., Peixoto, P. M. V., & Kitsis, R. N. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2303713120 · Cited by 42
“…translocator protein (also referred to as peripheral benzodiazepine receptor) (17), BCL2 associated X (BAX) and BCL2 antagonist/ killer 1 (BAK) (18, 19), adenine nucleotide translocase (ANT) (20, 21), the mitochondrial phosphate carrier (22), and cyclophilin D (11, 12) for Ca 2+ - induced mPTP…”
BackgroundSelf-citationAberrant Mitochondrial Fission Is Maladaptive in Desmin Mutation–Induced Cardiac Proteotoxicity
Alam, S., Abdullah, C. S., Aishwarya, R., Miriyala, S., Panchatcharam, M., Peretik, J. M., Orr, A. W., James, J., Robbins, J. M., & Bhuiyan, M. S. (2018) · Journal of the American Heart Association · doi:10.1161/jaha.118.009289 · Cited by 41
“Mitochondrial Ca Retention Capacity and Swelling Assay Mitochondrial Ca retention capacity was measured with Calcium Green 5N (Molecular Probes) as previously described.(22,23) Cardiac mitochondria (100 lg) were suspended in KCl buffer containing 125 mmol/L KCl, 20 mmol/ L HEPES, 2 mmol/L MgCl2, 2 mmol/L potassium pho…”
Self-citationBuskaran, K., Saifullah, B., Hussein, M. Z., Masarudin, M. J., Moklas, M. A. M., & Fakurazi, S. (2021) · Materials · doi:10.3390/ma14040817 · Cited by 41
“abundantly in cell cytosol will assist in the transportation of the protein through the mitochondrial membrane by stimulating the transition pore permeability [55].”
BackgroundChronic heart failure: Ca 2+ , catabolism, and catastrophic cell death
Cho, G. W., Altamirano, F. J., & Hill, J. A. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2016.01.011 · Cited by 40
“13 D- and Bax/Bak, both of which are known regulators of the MPTP, are resistant to necrotic cell death [114].”
BackgroundGan, I., Jiang, J., Lian, D., Huang, X., Fuhrmann, B., Liu, W., Haig, A. R., Jevnikar, A. M., & Zhang, Z. (2018) · American Journal of Transplantation · doi:10.1111/ajt.15112 · Cited by 38
Mitochondrial Fission Process 1 controls inner membrane integrity and protects against heart failure
Donnarumma, E., Kohlhaas, M., Vimont, E., Kornobis, É., Chaze, T., Gianetto, Q. G., Matondo, M., Moya‐Nilges, M., Maack, C., & Wai, T. (2022) · Nature Communications · doi:10.1038/s41467-022-34316-3 · Cited by 44
Chen, F., Xu, K., Han, Y., Ding, J., Ren, J., Wang, Y., Ma, Z., & Cao, F. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1503087 · Cited by 43
The c-Ring of the F1FO-ATP Synthase: Facts and Perspectives
Nesci, S., Trombetti, F., Ventrella, V., & Pagliarani, A. (2015) · The Journal of Membrane Biology · doi:10.1007/s00232-015-9860-3 · Cited by 40
Xu, L., Chen, L., Gu, G., Wang, Y., Xu, Y., & Zhong, Y.-G. (2022) · Reviews in Cardiovascular Medicine · doi:10.31083/j.rcm2302060 · Cited by 39
“The loss of mitochondrial membrane potential and a decrease in ATP synthesis can result, eventually inducing necrotic cell death [60].”
BackgroundBandaru, L. J. M., Ayyalasomayajula, N., Murumulla, L., & Challa, S. (2022) · BioMetals · doi:10.1007/s10534-021-00360-7 · Cited by 39
Directly targeting BAX for drug discovery: Therapeutic opportunities and challenges
Zhang, Z., Hou, L., Liu, D., Luan, S., Huang, M., & Zhao, L. (2024) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2024.02.010 · Cited by 42
“Emerging evidence indicates that BAX drives mitochondrial fusion 180 and MPTP-dependent Ca 2 þ release 181 to sensitize the opening of MPTP, ultimately promoting necrosis.”
BackgroundKerkhofs, M., Rovere, R. L., Welkenhuysen, K., Janssens, A. M., Vandenberghe, P., Madesh, M., Parys, J. B., & Bultynck, G. (2021) · Cell Calcium · doi:10.1016/j.ceca.2020.102333 · Cited by 38
Vimar Is a Novel Regulator of Mitochondrial Fission through Miro
Ding, L., Ye, L., Han, Y., Li, Y., Ji, X., & Liu, L. (2016) · PLoS Genetics · doi:10.1371/journal.pgen.1006359 · Cited by 36
“Necrotic cell death was induced by a calcium ionophore (A23187), which causes calcium overloading and necrosis [52].”
BackgroundDeragon, M. A., McCaig, W. D., Truong, P. V., Metz, K. R., Carron, K. A., Hughes, K. J., Knapp, A. R., Dougherty, M. J., & LaRocca, T. J. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24108609 · Cited by 38
“membrane in their non-oligomerized state [52,53].”
BackgroundLindblom, R. S. J., Higgins, G. C., Nguyen, T.-V., Arnstein, M., Henstridge, D. C., Granata, C., Snelson, M., Thallas‐Bonke, V., Cooper, M. E., Forbes, J. M., et al. (2020) · Clinical Science · doi:10.1042/cs20190787 · Cited by 36
In vitrocytotoxicity assessment of roundup (glyphosate) in L-02 hepatocytes
Luo, L., Wang, F., Zhang, Y., Zeng, M., Zhong, C., & Xiao, F. (2017) · Journal of Environmental Science and Health Part B · doi:10.1080/03601234.2017.1293449 · Cited by 35
“The opening of PTP is viewed as a critical event in the process of cell death.([19]) Calcium is a key element in metabolic and intracellular signaling regulation, and the concentration of Ca2C in the cytosol is tightly controlled under normal conditions.”
BackgroundLee, Y., Kwon, I., Jang, Y., Song, W., Cosío-Lima, L., & Roltsch, M. H. (2017) · The Journal of Physiological Sciences · doi:10.1007/s12576-017-0555-7 · Cited by 37
“Mitochondria are critical organelles that are required to provide a biological form of energy, namely, ATPs; however, once becoming dysfunctional, they can trigger apoptotic as well as necrotic cell death [10, 11].”
BackgroundAntoniak, S., Phungphong, S., Cheng, Z., & Jensen, B. C. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.817977 · Cited by 33
“In addition, Bax and Bak are necessary for mPTP-driven necrosis (64, 65).”
BackgroundSedky, N. K., Mahdy, N. K., Abdel-Kader, N. M., Abdelhady, M. M. M., Maged, M., Allam, A. L., Alfaifi, M. Y., Shamma, S. N., Hassan, H. A. F. M., & Fahmy, S. A. (2024) · RSC Advances · doi:10.1039/d3ra08908h · Cited by 31
Calcium uptake and cytochrome c release from normal and ischemic brain mitochondria
Andreyev, A. Y., Tamrakar, P., Rosenthal, R. E., & Fiskum, G. M. (2017) · Neurochemistry International · doi:10.1016/j.neuint.2017.10.003 · Cited by 34
“, the voltage dependent anion channel (VDAC), thereby promoting Ca2þ-dependent PTP opening (Morin et al., 2009; Karch et al., 2013; Whelan et al., 2012).”
Scruggs, S. B., Wang, D., & Ping, P. (2016) · Gene · doi:10.1016/j.gene.2016.06.016 · Cited by 33
“The new knowledge brings uncertainty regarding whether the inner and outer mitochondrial membranes physically couple during MPT; new models indicate that these function independently, with the primary site of regulation being on the inner membrane.”
InfluentialRegulated Necrosis in HeLa Cells Induced by ZnPc Photodynamic Treatment: A New Nuclear Morphology
Soriano, J., Villanueva, Á., STOCKERT, J. C., & Cañete, M. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms151222772 · Cited by 30
“Mitochondria would be also involved in this mechanism [36], but the integration of these processes is not yet known.”
BackgroundLenti-siRNA Hsp60 promote bax in mitochondria and induces apoptosis during heat stress
Song, E., Tang, S., Xu, J., Yin, B., Bao, E., & Hartung, J. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.10.153 · Cited by 30
The molecular mosaic of regulated cell death in the cardiovascular system
Martens, M. D., Karch, J. M., & Gordon, J. W. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2021.166297 · Cited by 31
Self-citationMitochondrial Volume Regulation and Swelling Mechanisms in Cardiomyocytes
Chapa‐Dubocq, X. R., Rodríguez‐Graciani, K. M., Escobales, N., & Javadov, S. A. (2023) · Antioxidants · doi:10.3390/antiox12081517 · Cited by 30
Guo, S., Zhou, J., Chen, X., Yu, Y., Ren, M., Hu, G., Liu, Y., & Zou, F. (2014) · Toxicology Letters · doi:10.1016/j.toxlet.2014.05.026 · Cited by 30
Brody, M. J., Schips, T. G., Vanhoutte, D., Kanisicak, O., Karch, J. M., Maliken, B. D., Blair, N. S., Sargent, M. A., Prasad, V., & Molkentin, J. D. (2015) · Molecular and Cellular Biology · doi:10.1128/mcb.00607-15 · Cited by 29
“Transmission electron microscopy (TEM) was performed as described previously (44).”
MethodSelf-citationPharmacological Targeting of Executioner Proteins: Controlling Life and Death
Pogmore, J. P., Uehling, D., & Andrews, D. W. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c02200 · Cited by 28
Noh, M. R., & Padanilam, B. J. (2024) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00275.2023 · Cited by 27
Yu, J. D., & Miyamoto, S. (2021) · Cells · doi:10.3390/cells10123330 · Cited by 25
“Although it has been disputed whether BAX/BAK regulates the mPTP opening, genetic studies revealed that deletion of BAX/BAK inhibits both the mPTP opening and necrotic cell death, suggesting the ability of BAX/BAK to facilitate mPTP-induced necrotic cell death [42,43].”
BackgroundMitochondrial oxidative stress, calcium and dynamics in cardiac ischaemia‐reperfusion injury
Rozich, E., Ozkurede, U., Pakkiriswami, S., Gemilere, R., Azarin, S. M., & Liu, J. C. (2025) · The Journal of Physiology · doi:10.1113/jp287770 · Cited by 29
“Other regulatory factors controlling mPTP opening include interactions between inner and outer mitochondrial membrane proteins, as well as the pro-apoptotic Bcl-2 family proteins Bax and Bak (Halestrap & Richardson, 2015; Karch et al., 2013; Patel et al., 2021; Whelan et al., 2012).”
[Retracted] Involvement of Mitochondrial Dynamics and Mitophagy in Sevoflurane‐Induced Cell Toxicity
Li, M., Guo, J., Wang, H., & Li, Y. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/6685468 · Cited by 23
RetractedLee, D., & Choi, J. (2021) · BioMed Research International · doi:10.1155/2021/9956938 · Cited by 20
Everett, K. D., Swain, L., Reyelt, L. A., Majumdar, M., Qiao, X., Bhave, S., Warner, M., Mahmoudi, E., Chin, M. T., Awata, J., et al. (2023) · JACC Basic to Translational Science · doi:10.1016/j.jacbts.2023.01.004 · Cited by 23
“As a result, loss of Bcl-2 during IRI allows Bax and Bak to create a second pore in the outer mitochondrial membrane that releases cytochrome C into the cytoplasm and activates caspasemediated cellular degradation via caspase-3.(28,29) Recent reports illustrate that stabilizing mitochondrial electron transport chain f…”
BackgroundArumugam, P., Samson, A. A. S., Ki, J., & Song, J. M. (2017) · Cell Biology and Toxicology · doi:10.1007/s10565-016-9378-1 · Cited by 23
“Recently, it has been reported that Bcl-2 family members, Bax and Bak, were critically required for the MPTP-dependent necrotic cell death (Karch andMolkentin 2015) (Karch et al. 2013).”
BackgroundDrees, A. A., Khalil, M. S., & Soliman, M. (2017) · ACTA HISTOCHEMICA ET CYTOCHEMICA · doi:10.1267/ahc.16025 · Cited by 26
Laser-mediated rupture of chlamydial inclusions triggers pathogen egress and host cell necrosis
Kerr, M. C., Gomez, G. A., Ferguson, C., Tanzer, M. C., Murphy, J. M., Yap, A. S., Parton, R. G., Huston, W. M., & Teasdale, R. D. (2017) · Nature Communications · doi:10.1038/ncomms14729 · Cited by 23
Su, L., Xu, J., Lu, C. C., Gao, K., Hu, Y., Xue, C., & Yan, X. (2024) · Cell Death Discovery · doi:10.1038/s41420-024-01947-y · Cited by 22
“In addition, the physical interaction of Bax/Bak with the mPTP constituents on the OMM can trigger mPT [8, 9].”
BackgroundMarzetti, E., Calvani, R., Landi, F., Coelho‐Júnior, H. J., & Picca, A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25137305 · Cited by 24
“RIP1/RIP3 phosphorylation also triggers mixed-lineage kinase domain-like protein (MLKL) activation [90,91], which guides mitochondrial disarrangement, altered cell permeability, and finally, necrosis [92].”
BackgroundDouble agents of cell death: novel emerging functions of apoptotic regulators
Lamb, H. M. (2020) · FEBS Journal · doi:10.1111/febs.15308 · Cited by 23
Drug delivery platforms for neonatal brain injury
Narayanamurthy, R., Yang, J. J., Yager, J. Y., & Unsworth, L. D. (2021) · Journal of Controlled Release · doi:10.1016/j.jconrel.2020.12.056 · Cited by 23
Pharmaceutical Therapies for Necroptosis in Myocardial Ischemia–Reperfusion Injury
Zhang, Y., Zhang, Y., Zang, J., Li, Y., & Wu, X. (2023) · Journal of Cardiovascular Development and Disease · doi:10.3390/jcdd10070303 · Cited by 24
“Many studies have investigated the pathogenesis of MI–RI, which is associated with oxidative stress, intracellular calcium overload, impaired energy metabolism [4,5], endoplasmic reticulum stress, apoptosis, necroptosis [6], autophagy [7,8], pyroptosis [9,10], and ferroptosis [11–13].”
BackgroundHwang, S., Kim, M., Ji, S., Yang, Y., Jeong, Y., & Kim, Y. (2019) · Cancer Science · doi:10.1111/cas.13952 · Cited by 23
Protective Effect of Morphine Against the Oxidant-Induced Injury in H9c2 Cells
Škrabalová, J., Karlovska, I., Hejnová, L., & Novotný, J. (2018) · Cardiovascular Toxicology · doi:10.1007/s12012-018-9448-0 · Cited by 21
Molecular mechanism and therapy application of necrosis during myocardial injury
Xu, T., Ding, W., Tariq, M., Wang, Y., Wan, Q., Li, M., & Wang, J. (2018) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.13575 · Cited by 22
“Mitochondrial permeability transition pore (MPTP) is a multiple protein complex modulating the opening of the inner mitochondrial membrane and allowing the passage of solutes with molecular weights 1500 Da.45 MPTP opening leads to the loss of ionic homeostasis, depleted ATP and ultimate necrotic cell death.46 The mole…”
BackgroundInfluentialDebernardi, J., Hollville, É., Lipinski, M., Wiels, J., & Robert, A. (2018) · Oncogene · doi:10.1038/s41388-018-0123-5 · Cited by 21
“Several studies have pointed towards a major role for BAX in CYT C release based on its ability to form channels in artificial lipid membranes [31, 32] and large oligomeric complexes in the mitochondrial outer membrane [33, 34].”
Mollinedo, F., & Gajate, C. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13050763 · Cited by 21
Patra, S., Mahapatra, K. K., Praharaj, P. P., Panigrahi, D. P., Bhol, C. S., Mishra, S. R., Behera, B. P., Singh, A., Jena, M., & Bhutia, S. K. (2021) · Mitochondrion · doi:10.1016/j.mito.2021.01.002 · Cited by 20
Saadeldin, I. M., Han, A., Bang, S., Kang, H., Kim, H., Abady, M. M., Jeong, J., Kwon, H., Lee, S., & Cho, J. (2023) · Reproduction · doi:10.1530/rep-23-0429 · Cited by 20
García-Belinchón, M., Sánchez‐Osuna, M., Martínez‐Escardó, L., Granados-Colomina, C., Pascual-Guiral, S., Iglesias‐Guimarais, V., Casanelles, E., Ribas, J., & Yuste, V. J. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.644179 · Cited by 20
“Indeed, similarly to H2O2 but contrarily to staurosporine, chelerythrine increased the percentage of annexin V/PI-double stained (late apoptotic/early necrotic) cells from early times (between 1 and 3 h) of treatment (Fig.”
BackgroundInfluentialGao, Y., Zhang, D., Wang, F., Zhang, D., Li, P., & Wang, K. (2022) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.17443 · Cited by 19
Liu, G., Lv, Y., Wang, Y., Xu, Z., Chen, L., Chen, S., Xie, W., Feng, Y., Liu, J., Bai, Y., et al. (2023) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2023.12.030 · Cited by 19
Tawfeek, S. E., Domouky, A. M., & Abdel-Kareem, R. H. (2021) · Anatomy & Cell Biology · doi:10.5115/acb.21.124 · Cited by 18
“In addition, Bax is responsible for the formation of these permeability pores leading to cell necrosis [52].”
BackgroundWu, T., Tong, M., Chu, A., Wu, K., Niu, X., & Zhang, Z. (2022) · Cardiovascular Toxicology · doi:10.1007/s12012-022-09753-7 · Cited by 18
“It has been shown that the pathological opening of mPTP is involved in the occurrence of myocardial ischemia/ reperfusion injury and heart failure [19, 20].”
BackgroundHe, L., & Maheshwari, A. (2022) · Current Pediatric Reviews · doi:10.2174/1573396319666221221110728 · Cited by 17
Zhang, W., Liu, N., Wang, X., Jin, X., Du, H., Peng, G., & Xue, J. F. (2014) · Human & Experimental Toxicology · doi:10.1177/0960327114533358 · Cited by 18
“The onset of mitochondrial permeability transition pore was involved in necrosis.(15) Apoptosis and necrosis can occur concurrently and share some common pathways, which may be differentially induced by variable doses of pollutants.”
BackgroundCell death mechanisms in human chronic liver diseases: a far cry from clinical applicability
Mazzolini, G. D., Sowa, J., & Canbay, A. E. (2016) · Clinical Science · doi:10.1042/cs20160035 · Cited by 18
Zhou, Y., Zhang, H., Yan, H., Han, P., Zhang, J., & Liu, Y. (2025) · Frontiers in Bioscience-Landmark · doi:10.31083/fbl27046 · Cited by 26
“These proteins oligomerize or interact with the mitochondrial permeability transition pore to form channels [124].”
Zhang, X., Li, S., Zheng, M., Zhang, L., Bai, R., Li, R., Hao, S., Bai, B., & Kang, H. (2020) · Parasitology Research · doi:10.1007/s00436-020-06738-9 · Cited by 17
“After being stimulated by apoptotic signal, bad is dephosphorylated, and free bad is promoted by replacing Bax on the Bcl-2/Bax and Bcl-Lx/Bax dimers through the above mechanism to promote apoptosis (Karch et al. 2013).”
BackgroundFUNDC1-mediated mitophagy regulates photodamage independently of the PINK1/Parkin-dependent pathway
He, H., Huang, W., Xiong, L., Ma, C., Wang, Y., Sun, P., Shi, D., Li, L., Yan, H., & Wu, Y. (2024) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2024.10.272 · Cited by 17
Colella, F., Scillitani, G., & Pierri, C. L. (2020) · Toxicology · doi:10.1016/j.tox.2020.152612 · Cited by 17
Ramachandran, R., & Saraswathy, M. (2017) · Cardiovascular Therapeutics · doi:10.1111/1755-5922.12279 · Cited by 17
Jing, Y., Zhang, Y., Kadier, T., Ding, K., Chen, R., & Meng, Q. (2025) · Cell Communication and Signaling · doi:10.1186/s12964-025-02603-3 · Cited by 15
Hepatoprotective role of liver fatty acid binding protein in acetaminophen induced toxicity
Gong, Y., Wang, G., Gong, Y., Yan, J., Chen, Y. A., & Burczynski, F. J. (2014) · BMC Gastroenterology · doi:10.1186/1471-230x-14-44 · Cited by 15
“Thus, Bax may modulate necrosis through mechanisms that are distinct from apoptosis [26,27].”
BackgroundKamradt, M. L., & Makarewich, C. A. (2023) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00189.2023 · Cited by 15
Patel, P., Mendoza, A., Ramirez, D., Robichaux, D. J., Molkentin, J. D., & Karch, J. M. (2024) · Science Advances · doi:10.1126/sciadv.adp7444 · Cited by 19
Self-citationAydınlık, Ş., Dere, E., & Ulukaya, E. (2019) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2019.02.014 · Cited by 15
Ma, Z., Liu, C., Zhang, L., Xiang, N., Zhang, Y., & Chu, L. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.806200 · Cited by 15
“The C-fos level can then gradually return to normal levels within 24 h (Karch et al., 2013; Nikoletopoulou et al., 2013).”
BackgroundShi, X., Yin, Y., Guo, X., Liu, M., Ma, F., Li, T. X., Zheng, M., & Liu, G. (2023) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2023.05.120 · Cited by 13
Xu, M., Zhu, J., Wang, Z., Yan, J., & Zhou, X. (2024) · Mitochondrion · doi:10.1016/j.mito.2024.101924 · Cited by 13
Toxic oligomers of the amyloidogenic HypF-N protein form pores in mitochondrial membranes
Farrugia, M. Y., Caruana, M., Ghio, S., Camilleri, A., Farrugia, C., Cauchi, R. J., Cappelli, S., Chiti, F., & Vassallo, N. (2020) · Scientific Reports · doi:10.1038/s41598-020-74841-z · Cited by 13
Harvey, K. L., Hussain, A., & Maddock, H. L. (2014) · Toxicological Sciences · doi:10.1093/toxsci/kfu001 · Cited by 13
Selective BH3-mimetics targeting BCL-2, BCL-XL or MCL-1 induce severe mitochondrial perturbations
Henz, K., Al-Zebeeby, A., Başoğlu, M., Fulda, S., Cohen, G. M., Varadarajan, S., & Vogler, M. (2018) · Biological Chemistry · doi:10.1515/hsz-2018-0233 · Cited by 13
“Upon PTP opening, small solutes and water move osmotically into the mitochondrial matrix, thus causing swelling and rupture of the outer mitochondrial membrane (Bernardi et al., 2006).”
BackgroundInfluentialLiver-specific Bid silencing inhibits APAP-induced cell death in mice
Maxa, M., Schaeper, U., Dames, S., Vollmar, B., & Kuhla, A. (2019) · APOPTOSIS · doi:10.1007/s10495-019-01571-7 · Cited by 13
Caruana, M., Camilleri, A., Farrugia, M. Y., Ghio, S., Jakubíčková, M., Cauchi, R. J., & Vassallo, N. (2021) · Molecules · doi:10.3390/molecules26051444 · Cited by 13
“A convenient and frequently used assay to monitor mitochondrial swelling involves measuring the turbidity in mitochondrial suspensions (A540) [38].”
MethodStulczewski, D., Zgórzyńska, E., Dziedzic, B., Wieczorek, K., Szafraniec, K., & Walczewska, A. (2023) · Experimental Cell Research · doi:10.1016/j.yexcr.2023.113491 · Cited by 15
The Mitochondrial Permeability Transition Pore
Morganti, C., Bonora, M., Sbano, L., Morciano, G., Aquila, G., Campo, G. C., Wieckowski, M. R., Giorgi, C., & Pinton, P. (2018) · Springer eBooks · doi:10.1007/978-3-319-73344-9_5 · Cited by 13
Metadata
- Authors
- Karch, J., Kwong, J. Q., Burr, A. R., Sargent, M. A., Elrod, J. W., Peixoto, P. M., Martinez-Caballero, S., Osinska, H., Cheng, E. H.-Y., Robbins, J., Kinnally, K. W., & Molkentin, J. D.
- Affiliations
- Cincinnati Children's Hospital Medical Center (US)
- New York University (US)
- Department of Basic Sciences, New York University College of Dentistry, New York, United States
- Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati, Cincinnati, United States
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Molkentin, Jeffery D
- ORCID
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2013-08-27
- Volume
- 2
- Pages
- e00772-e00772
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC3755340
- OpenAlex
- W2139284714
- Cited by
- 290
- References
- 53
- Citations by year
- 2026: 8 · 2025: 25 · 2024: 16 · 2023: 31 · 2022: 22 · 2021: 26 · 2020: 25 · 2019: 23 · 2018: 27 · 2017: 22 · 2016: 26 · 2015: 16 · 2014: 21 · 2013: 1
- FWCI
- 9.55
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- CUNY Academic Works (City University of New York) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (P01 HL080101)
- American Heart Association pre-doctoral grant
- American Heart Association
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Ischemia and Reperfusion
- Keywords
- Bax, Bak, mitochondrial permeability transition pore, necrosis, mitochondrial outer membrane permeabilization, Bcl-2 family proteins, mitochondrial calcium overload, mitochondrial swelling, ischemia, Bax oligomerization
- MeSH terms
- Mitochondrial Permeability Transition Pore, Animals, Necrosis, Mitochondrial Membrane Transport Proteins, bcl-2 Homologous Antagonist-Killer Protein, bcl-2-Associated X Protein, Mice
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
