The DOI matches its Crossref record; 50 of the 51 references it cites were found in a registry or an index.
Mitochondrial Shape Governs BAX-Induced Membrane Permeabilization and Apoptosis
Open accessAbstract
Proapoptotic BCL-2 proteins converge upon the outer mitochondrial membrane (OMM) to promote mitochondrial outer membrane permeabilization (MOMP) and apoptosis. Here we investigated the mechanistic relationship between mitochondrial shape and MOMP and provide evidence that BAX requires a distinct mitochondrial size to induce MOMP. We utilized the terminal unfolded protein response pathway to systematically define proapoptotic BCL-2 protein composition after stress and then directly interrogated their requirement for a productive mitochondrial size. Complementary biochemical, cellular, in vivo, and ex vivo studies reveal that Mfn1, a GTPase involved in mitochondrial fusion, establishes a mitochondrial size that is permissive for proapoptotic BCL-2 family function. Cells with hyperfragmented mitochondria, along with size-restricted OMM model systems, fail to support BAX-dependent membrane association and permeabilization due to an inability to stabilize BAXα9·membrane interactions. This work identifies a mechanistic contribution of mitochondrial size in dictating BAX activation, MOMP, and apoptosis.
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
“Finally, it is becoming increasingly evident that mitochondrial size and shape [139–141] as well as lipid composition [142, 143] can influence the likelihood of mitochondria to undergo irreversible MOMP.”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [140]
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
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
Mitochondrial Fission, Fusion, and Stress
Youle, R. J., & van der Bliek, A. M. (2012) · Science · doi:10.1126/science.1219855 · Cited by 3,674
An inhibitor of Bcl-2 family proteins induces regression of solid tumours
Oltersdorf, T., Elmore, S. W., Shoemaker, A. R., Armstrong, R. C., Augeri, D. J., Belli, B., Bruncko, M., Deckwerth, T. L., Dinges, J., Hajduk, P. J., et al. (2005) · Nature · doi:10.1038/nature03579 · Cited by 3,407
Regulated Translation Initiation Controls Stress-Induced Gene Expression in Mammalian Cells
Harding, H. P., Novoa, I., Zhang, Y., Zeng, H., Wek, R. C., Schapira, M., & Ron, D. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)00108-8 · Cited by 3,344
Chen, H., Detmer, S. A., Ewald, A. J., Griffin, E. E., Fraser, S. E., & Chan, D. C. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200211046 · Cited by 2,601
Mitofusin 2 tethers endoplasmic reticulum to mitochondria
de Brito, O. M., & Scorrano, L. (2008) · Nature · doi:10.1038/nature07534 · Cited by 2,442
Letai, A., Bassik, M. C., Walensky, L. D., Sorcinelli, M. D., Weiler, S., & Korsmeyer, S. J. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00127-7 · Cited by 1,677
Bid, Bax, and Lipids Cooperate to Form Supramolecular Openings in the Outer Mitochondrial Membrane
Kuwana, T., Mackey, M. R., Perkins, G. A., Ellisman, M. H., Latterich, M., Schneiter, R., Green, D. R., & Newmeyer, D. D. (2002) · Cell · doi:10.1016/s0092-8674(02)01036-x · Cited by 1,513
Self-citationER Stress Triggers Apoptosis by Activating BH3-Only Protein Bim
Puthalakath, H., O’Reilly, L. A., Gunn, P., Lee, L., Kelly, P. N., Huntington, N. D., Hughes, P., Michalak, E. M., McKimm‐Breschkin, J. L., Motoyama, N., et al. (2007) · Cell · doi:10.1016/j.cell.2007.04.027 · Cited by 1,493
Chipuk, J. E., Moldoveanu, T., Llambi, F., Parsons, M. J., & Green, D. R. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.01.025 · Cited by 1,476
Self-citationIRE1 Signaling Affects Cell Fate During the Unfolded Protein Response
Lin, J. H., Li, H., Yasumura, D., Cohen, H., Zhang, C., Panning, B., Shokat, K., Lavail, M., & Walter, P. (2007) · Science · doi:10.1126/science.1146361 · Cited by 1,435
Mitochondria in Apoptosis: Bcl-2 Family Members and Mitochondrial Dynamics
Martinou, J., & Youle, R. J. (2011) · Developmental Cell · doi:10.1016/j.devcel.2011.06.017 · Cited by 1,395
Csordás, G., Renken, C. W., Várnai, P., Walter, L., Weaver, D., BUTTLE, K. F., Balla, T., Mannella, C. A., & Hajnóczky, G. (2006) · The Journal of Cell Biology · doi:10.1083/jcb.200604016 · Cited by 1,377
Translational Control Is Required for the Unfolded Protein Response and In Vivo Glucose Homeostasis
Scheuner, D. L., Song, B., McEwen, E. L., Liu, C., Laybutt, D. R., Gillespie, P. J., Saunders, T. L., Bonner‐Weir, S., & Kaufman, R. J. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00265-9 · Cited by 1,355
tBID, a membrane-targeted death ligand, oligomerizes BAK to release cytochrome cPreprint
Wei, M. C., Lindsten, T., Mootha, V. K., Weiler, S., Gross, A., Ashiya, M., Thompson, C. B., & Korsmeyer, S. J. (2000) · Genes & Development · doi:10.1101/gad.14.16.2060 · Cited by 1,292
Certo, M. V., Moore, V. D. G., Nishino, M., Wei, G., Korsmeyer, S. J., Armstrong, S. A., & Letai, A. G. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.03.027 · Cited by 1,278
Cogliati, S., Frezza, C., Soriano, M. E., Varanita, T., Quintana-Cabrera, R., Corrado, M., Cipolat, S., Costa, V., Casarin, A., Gomes, L. C., et al. (2013) · Cell · doi:10.1016/j.cell.2013.08.032 · Cited by 1,265
Cassidy-Stone, A., Chipuk, J. E., Ingerman, E., Song, C., Yoo, C., Kuwana, T., Kurth, M. J., Shaw, J. T., Hinshaw, J. E., Green, D. R., et al. (2008) · Developmental Cell · doi:10.1016/j.devcel.2007.11.019 · Cited by 1,200
Self-citationKuwana, T., Bouchier-Hayes, L., Chipuk, J. E., Bonzon, C., Sullivan, B. A., Green, D. R., & Newmeyer, D. D. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.02.003 · Cited by 1,185
Self-citationSuzuki, M., Youle, R. J., & Tjandra, N. (2000) · Cell · doi:10.1016/s0092-8674(00)00167-7 · Cited by 1,104
Puma is an essential mediator of p53-dependent and -independent apoptotic pathways
Jeffers, J. R., Parganas, E., Lee, Y., Yang, C., Wang, J., Brennan, J. A., Maclean, K. H., Han, J., Chittenden, T., Ihle, J. N., et al. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00244-7 · Cited by 880
Conformation of the Bax C‐terminus regulates subcellular location and cell death
Nechushtan, A., Smith, C. L., Hsu, Y., & Youle, R. J. (1999) · The EMBO Journal · doi:10.1093/emboj/18.9.2330 · Cited by 732
Endoplasmic Reticulum Stress Sensing in the Unfolded Protein ResponsePreprint
Gardner, B. M., Pincus, D., Gotthardt, K., Gallagher, C. M., & Walter, P. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a013169 · Cited by 716
Moore, V. D. G., Brown, J. R., Certo, M. V., Love, T. M., Novina, C. D., & Letai, A. G. (2007) · Journal of Clinical Investigation · doi:10.1172/jci28281 · Cited by 617
Nonionic Detergents Induce Dimerization among Members of the Bcl-2 Family
Hsu, Y., & Youle, R. J. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.21.13829 · Cited by 591
The ER function BiP is a master regulator of ER function.
Hendershot, L. M. (2004) · PubMed · Cited by 439
Membrane Remodeling Induced by the Dynamin-Related Protein Drp1 Stimulates Bax Oligomerization
Montessuit, S., Somasekharan, S. P., Terrones, O., Lucken‐Ardjomande, S., Herzig, S., Schwarzenbacher, R., Manstein, D. J., Bossy‐Wetzel, E., Basáñez, G., Meda, P., et al. (2010) · Cell · doi:10.1016/j.cell.2010.08.017 · Cited by 437
Chipuk, J. E., McStay, G. P., Bharti, A., Kuwana, T., Clarke, C. J., Siskind, L. J., Obeid, L. M., & Green, D. R. (2012) · Cell · doi:10.1016/j.cell.2012.01.038 · Cited by 436
Self-citationGene expression during ER stress–induced apoptosis in neurons
Reimertz, C., Kögel, D., Rami, A., Chittenden, T., & Prehn, J. H. M. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200305149 · Cited by 373
Sarosiek, K. A., Chi, X., Bachman, J. A., Sims, J. J., Montero, J., Patel, L., Flanagan, A., Andrews, D. W., Sorger, P. K., & Letai, A. G. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.08.048 · Cited by 252
Preservation of Mitochondrial Structure and Function after Bid- or Bax-Mediated Cytochrome c Release
von Ahsen, O., Renken, C. W., Perkins, G. A., Kluck, R. M., Bossy‐Wetzel, E., & Newmeyer, D. D. (2000) · The Journal of Cell Biology · doi:10.1083/jcb.150.5.1027 · Cited by 245
Self-citationMechanism of apoptosis induction by inhibition of the anti-apoptotic BCL-2 proteins
Chipuk, J. E., Fisher, J. C., Dillon, C. P., Kriwacki, R. W., Kuwana, T., & Green, D. R. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808036105 · Cited by 245
Self-citationExpression, purification and use of recombinant annexin V for the detection of apoptotic cells
Logue, S. E., Elgendy, M., & Martin, S. J. (2009) · Nature Protocols · doi:10.1038/nprot.2009.143 · Cited by 242
Ghosh, A. P., Klocke, B. J., Ballestas, M. E., & Roth, K. A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0039586 · Cited by 233
Resistance to Caspase-Independent Cell Death Requires Persistence of Intact Mitochondria
Tait, S. W. G., Parsons, M. J., Llambi, F., Bouchier‐Hayes, L., Connell, S., Muñoz‐Pinedo, C., & Green, D. R. (2010) · Developmental Cell · doi:10.1016/j.devcel.2010.03.014 · Cited by 204
Yethon, J. A., Epand, R. F., Leber, B. F., Epand, R. M., & Andrews, D. W. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m306289200 · Cited by 203
Life and death of a BiP substrate
Otero, J. H., Lizák, B., & Hendershot, L. M. (2009) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2009.12.008 · Cited by 188
Dorner, A. J., Wasley, L. C., Raney, P., Haugejorden, S. M., Green, M., & Kaufman, R. J. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)45843-7 · Cited by 185
Loss of Mitofusin 2 Promotes Endoplasmic Reticulum Stress
Ngoh, G. A., Papanicolaou, K. N., & Walsh, K. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.359174 · Cited by 183
BH3 profiling in whole cells by fluorimeter or FACS
Ryan, J. A., & Letai, A. G. (2013) · Methods · doi:10.1016/j.ymeth.2013.04.006 · Cited by 174
Mitochondrial Dynamics and Apoptosis—the ER Connection
Hoppins, S. C., & Nunnari, J. M. (2012) · Science · doi:10.1126/science.1224709 · Cited by 137
Contributions to Bax insertion and oligomerization of lipids of the mitochondrial outer membrane
Lucken‐Ardjomande, S., Montessuit, S., & Martinou, J. (2008) · Cell Death and Differentiation · doi:10.1038/cdd.2008.9 · Cited by 136
Yamaguchi, R., Andreyev, A. Y., Murphy, A. N., Perkins, G. A., Ellisman, M. H., & Newmeyer, D. D. (2006) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4402035 · Cited by 135
Self-citationPrice, B. D., Mannheim‐Rodman, L. A., & Calderwood, S. K. (1992) · Journal of Cellular Physiology · doi:10.1002/jcp.1041520314 · Cited by 99
Kushnareva, Y., Andreyev, A. Y., Kuwana, T., & Newmeyer, D. D. (2012) · PLoS Biology · doi:10.1371/journal.pbio.1001394 · Cited by 94
Self-citationBeverly, L. J., Howell, L. A., Hernandez‐Corbacho, M. J., Casson, L. K., Chipuk, J. E., & Siskind, L. J. (2013) · Biochemical Journal · doi:10.1042/bj20130147 · Cited by 52
Self-citationGenetically defining the mechanism of Puma- and Bim-induced apoptosis
Garrison, S. P., Phillips, D. C., Jeffers, J. R., Chipuk, J. E., Parsons, M. J., Rehg, J. E., Opferman, J. T., Green, D. R., & Zambetti, G. P. (2011) · Cell Death and Differentiation · doi:10.1038/cdd.2011.136 · Cited by 40
Self-citationBlobel, G. A. (2000) · Bioscience Reports · doi:10.1023/a:1010318832604 · Cited by 29
Examining BCL-2 Family Function with Large Unilamellar Vesicles
Asciolla, J. J., Renault, T. T., & Chipuk, J. E. (2012) · Journal of Visualized Experiments · doi:10.3791/4291 · Cited by 24
Self-citationExamining BCL-2 Family Function with Large Unilamellar Vesicles
Asciolla, J. J., Renault, T. T., & Chipuk, J. E. (2012) · Journal of Visualized Experiments · doi:10.3791/4291-v · Cited by 7
Self-citation
Flagged first, then by citations
1 of the 51 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Galluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., et al. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0012-4 · Cited by 6,680
Self-citationTargeting apoptosis in cancer therapy
Carneiro, B. A., & El‐Deiry, W. S. (2020) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-020-0341-y · Cited by 2,676
Vyas, S., Zaganjor, E., & Haigis, M. C. (2016) · Cell · doi:10.1016/j.cell.2016.07.002 · Cited by 1,735
Bax, Bak and beyond — mitochondrial performance in apoptosis
Peña‐Blanco, A., & García‐Sáez, A. J. (2017) · FEBS Journal · doi:10.1111/febs.14186 · Cited by 987
Pernas, L. F., & Scorrano, L. (2015) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021115-105011 · Cited by 845
Metadata
- Authors
- Renault, T. T., Floros, K. V., Elkholi, R., Corrigan, K.-A., Kushnareva, Y., Wieder, S. Y., Lindtner, C., Serasinghe, M. N., Asciolla, J. J., Buettner, C., Newmeyer, D. D., & Chipuk, J. E.
- Affiliations
- Tisch Cancer Institute (US)
- Icahn School of Medicine at Mount Sinai (US)
- La Jolla Institute for Immunology (US)
- Mount Sinai Hospital (US)
- Corresponding author
- Chipuk, Jerry E.
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2015-01
- Volume
- 57
- Issue
- 1
- Pages
- 69-82
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC4289414
- OpenAlex
- W2049807952
- Cited by
- 217
- References
- 51
- Citations by year
- 2026: 13 · 2025: 11 · 2024: 13 · 2023: 14 · 2022: 20 · 2021: 23 · 2020: 22 · 2019: 21 · 2018: 18 · 2017: 23 · 2016: 24 · 2015: 15
- FWCI
- 8.48
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Rutgers University Community Repository (Rutgers University) (submittedVersion)
- Funders
- National Institutes of Health (5r01aa023416-04)
- National Institute on Alcohol Abuse and Alcoholism (NIH P20AA017067, P20AA017067, R01-AA-023416)
- National Cancer Institute (CA157740, R01CA157740)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK083568, R03DK082724, K08DK074873, DK-082724)
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- mitochondrial morphology, mitochondrial size, Bax, mitochondrial outer membrane permeabilization, apoptosis, Bcl-2 family proteins, Mfn1, mitochondrial fusion, mitochondrial outer membrane
- MeSH terms
- Bcl-2-Like Protein 11, Animals, Gene Expression Regulation, Membrane Proteins, Mitochondria, Liver, Permeability, Proto-Oncogene Proteins, Signal Transduction, Apoptosis, GTP Phosphohydrolases, bcl-2 Homologous Antagonist-Killer Protein, Apoptosis Regulatory Proteins, bcl-2-Associated X Protein, Mitochondrial Membranes, Mice, Membrane Potential, Mitochondrial, Organelle Shape, Unilamellar Liposomes, Mitochondrial Dynamics
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
