Bcl-xL Prevents Cell Death following Growth Factor Withdrawal by Facilitating Mitochondrial ATP/ADP Exchange
Open accessAbstract
Growth factor withdrawal is associated with a metabolic arrest that can result in apoptosis. Cell death is preceded by loss of outer mitochondrial membrane integrity and cytochrome c release. These mitochondrial events appear to follow a relative increase in mitochondrial membrane potential. This change in membrane potential results from the failure of the adenine nucleotide translocator (ANT)/voltage-dependent anion channel (VDAC) complex to maintain ATP/ADP exchange. Bcl-xL expression allows growth factor-deprived cells to maintain sufficient mitochondrial ATP/ADP exchange to sustain coupled respiration. These data demonstrate that mitochondrial adenylate transport is under active regulation. Efficient exchange of ADP for ATP is promoted by Bcl-xL expression permitting oxidative phosphorylation to be regulated by cellular ATP/ADP levels and allowing mitochondria to adapt to changes in metabolic demand.
Integrity signals
Registry
Cites
Statistics
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?
Pro- and anti-apoptotic BCL2 family members such as BAX, BAK, BID, BCL2, and BCL-XL regulate MPT-driven necrosis.
“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 [414]
Cites
Li, P., Nijhawan, D., Budihardjo, I., Srinivasula, S. M., Ahmad, M., Alnemri, E. S., & Wang, X. (1997) · Cell · doi:10.1016/s0092-8674(00)80434-1 · Cited by 7,289 · see citing works
Prevention of Apoptosis by Bcl-2: Release of Cytochrome c from Mitochondria Blocked
Yang, J., Liu, X., Bhalla, K. N., Kim, C. N., Ibrado, A. M., Cai, J., Peng, T.-I., Jones, D. P., & Wang, X. (1997) · Science · doi:10.1126/science.275.5303.1129 · Cited by 4,913 · see citing works
The Release of Cytochrome c from Mitochondria: A Primary Site for Bcl-2 Regulation of Apoptosis
Kluck, R. M., Bossy‐Wetzel, E., Green, D. R., & Newmeyer, D. D. (1997) · Science · doi:10.1126/science.275.5303.1132 · Cited by 4,715 · see citing works
Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death
Hockenbery, D., Nuñez, G., Milliman, C., Schreiber, R. D., & Korsmeyer, S. J. (1990) · Nature · doi:10.1038/348334a0 · Cited by 3,720 · see citing works
Bcl-2 functions in an antioxidant pathway to prevent apoptosis
Hockenbery, D. M., Oltvai, Z. N., Yin, X., Milliman, C. L., & Korsmeyer, S. J. (1993) · Cell · doi:10.1016/0092-8674(93)80066-n · Cited by 3,420 · see citing works
Zou, H., Henzel, W. J., Liu, X., Lutschg, A., & Wang, X. (1997) · Cell · doi:10.1016/s0092-8674(00)80501-2 · Cited by 3,145 · see citing works
bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death
Boise, L., González‐García, M., Postema, C. E., Ding, L., Lindsten, T., Turka, L. A., Mao, X., Núñez, G., & Thompson, C. B. (1993) · Cell · doi:10.1016/0092-8674(93)90508-n · Cited by 3,089 · see citing works
Self-citationProgrammed Cell Death in Animal Development
Jacobson, M. D., Weil, M., & RAFF, M. C. (1997) · Cell · doi:10.1016/s0092-8674(00)81873-5 · Cited by 2,685 · see citing works
Social controls on cell survival and cell death
RAFF, M. C. (1992) · Nature · doi:10.1038/356397a0 · Cited by 2,634 · see citing works
The proto-oncogene Bcl-2 and its role in regulating apoptosis
Kroemer, G. (1997) · Nature Medicine · doi:10.1038/nm0697-614 · Cited by 1,739 · see citing works
Bcl-2 inhibition of neural death: decreased generation of reactive oxygen species
Kane, D. J., Sarafian, T. A., Anton, R., Hahn, H., Gralla, E. B., Valentine, J. S., Örd, T., & Bredesen, D. E. (1993) · Science · doi:10.1126/science.8235659 · Cited by 1,671 · see citing works
Bax directly induces release of cytochrome c from isolated mitochondria
Jürgensmeier, J. M., Xie, Z., Deveraux, Q. L., Ellerby, L., Bredesen, D. E., & Reed, J. C. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.9.4997 · Cited by 1,523 · see citing works
X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death
Muchmore, S. W., Sattler, M., Liang, H., Meadows, R. P., Harlan, J. E., Yoon, H. S., Nettesheim, D. G., Chang, B. S., Thompson, C. B., Wong, S., et al. (1996) · Nature · doi:10.1038/381335a0 · Cited by 1,467 · see citing works
Self-citationBcl-xL Regulates the Membrane Potential and Volume Homeostasis of Mitochondria
Heiden, M. G. V., Chandel, N. S., Williamson, E. K., Schumacker, P. T., & Thompson, C. B. (1997) · Cell · doi:10.1016/s0092-8674(00)80450-x · Cited by 1,378 · see citing works
Self-citationInhibition of Bax Channel-Forming Activity by Bcl-2
Antonsson, B. E., Conti, F., Ciavatta, A., Montessuit, S., Lewis, S., Martinou, I., Bernasconi, L., Bernard, A., Mermod, J., Mazzei, G. J., et al. (1997) · Science · doi:10.1126/science.277.5324.370 · Cited by 1,028 · see citing works
Bcl-xL forms an ion channel in synthetic lipid membranes
Minn, A. J., Vélez, P., Schendel, S. L., Liang, H., Muchmore, S. W., Fesik, S. W., Fill, M., & Thompson, C. B. (1997) · Nature · doi:10.1038/385353a0 · Cited by 814 · see citing works
Self-citationThe central executioners of apoptosis: caspases or mitochondria?
Green, D. R., & Kroemer, G. (1998) · Trends in Cell Biology · doi:10.1016/s0962-8924(98)01273-2 · Cited by 775 · see citing works
Bcl-2 blocks apoptosis in cells lacking mitochondrial DNA
Jacobson, M. D., Burne, J. F., King, M. P., Miyashrta, T., Reed, J. C., & RAFF, M. C. (1993) · Nature · doi:10.1038/361365a0 · Cited by 751 · see citing works
Channel formation by antiapoptotic protein Bcl-2
Schendel, S. L., Xie, Z., Oblatt-Montal, M., Matsuyama, S., Montal, M., & Reed, J. C. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.10.5113 · Cited by 602 · see citing works
Control of respiration and ATP synthesis in mammalian mitochondria and cells
Brown, G. C. (1992) · Biochemical Journal · doi:10.1042/bj2840001 · Cited by 598 · see citing works
Akt Signaling--Linking Membrane Events to Life and Death Decisions
Hemmings, B. A. (1997) · Science · doi:10.1126/science.275.5300.628 · Cited by 517 · see citing works
Apoptosis induced in Jurkat cells by several agents is preceded by intracellular acidification.
Gottlieb, R. A., Nordberg, J., Skowronski, E. W., & BABIOR, B. M. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.2.654 · Cited by 495 · see citing works
Regulation of cellular energy metabolism
Erecińska, M., & Wilson, D. F. (1982) · The Journal of Membrane Biology · doi:10.1007/bf01871584 · Cited by 442 · see citing works
Rostovtseva, T. K., & Colombini, M. (1997) · Biophysical Journal · doi:10.1016/s0006-3495(97)78841-6 · Cited by 357 · see citing works
Zhu, W., Cowie, A., Wasfy, G. W., Penn, L. Z., Leber, B. F., & Andrews, D. W. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00788.x · Cited by 327 · see citing works
Maintenance of Calcium Homeostasis in the Endoplasmic Reticulum by Bcl-2
He, H., Lam, M. C., McCormick, T. S., & Distelhorst, C. (1997) · The Journal of Cell Biology · doi:10.1083/jcb.138.6.1219 · Cited by 296 · see citing works
Buchet, K., & Godinot, C. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.36.22983 · Cited by 231 · see citing works
Energy Metabolism during Apoptosis
Garland, J. M., & Halestrap, A. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.8.4680 · Cited by 207 · see citing works
Oxygen conformance of cellular respiration in hepatocytes
Schumacker, P. T., Chandel, N. S., & Agustí, A. G. N. (1993) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.1993.265.4.l395 · Cited by 148 · see citing works
Self-citationMetabolic and Structural States of Mitochondria
Packer, L. (1960) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)69618-8 · Cited by 147 · see citing works
Apoptosis is regulated by the rate of glucose transport in an interleukin 3 dependent cell line.
Kan, O., Baldwin, S. A., & Whetton, A. D. (1994) · The Journal of Experimental Medicine · doi:10.1084/jem.180.3.917 · Cited by 112 · see citing works
The ‘ins’ and ‘outs’ of mitochondrial membrane channels
Mannella, C. A. (1992) · Trends in Biochemical Sciences · doi:10.1016/0968-0004(92)90444-e · Cited by 99 · see citing works
ADP/ATP translocator is essential only for anaerobic growth of yeast Saccharomyces cerevisiae
Drgon, T., Sabová, L., Nelson, N., et al. (1991) · FEBS Letters · doi:10.1016/0014-5793(91)81059-h · Cited by 89 · see citing works
The contribution of ATP turnover by the Na+/K+-ATPase to the rate of respiration of hepatocytes
Nobes, C. D., Lakin‐Thomas, P. L., & Brand, M. D. (1989) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/s0005-2728(89)80236-1 · Cited by 55 · see citing works
Šubík, J., Kolarov, J., & Kováč, L. (1974) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/0005-2728(74)90036-x · Cited by 26 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation
Vander Heiden, M. G., Cantley, L. C., & Thompson, C. B. (2009) · Science · doi:10.1126/science.1160809 · Cited by 16,197 · see citing works
Self-citationGalluzzi, 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 · see citing works
Self-citationCellular survival: a play in three Akts
Datta, S. R., Brunet, A., & Greenberg, M. E. (1999) · Genes & Development · doi:10.1101/gad.13.22.2905 · Cited by 4,216 · see citing works
Mitochondrial membrane permeabilization in cell death
Kroemer, G., Galluzzi, L., & Brenner, C. (2007) · Physiological Reviews · doi:10.1152/physrev.00013.2006 · Cited by 3,598 · see citing works
Mitochondrial control of cell death
Kroemer, G., & Reed, J. C. (2000) · Nature Medicine · doi:10.1038/74994 · Cited by 3,103 · see citing works
Growth factor regulation of autophagy and cell survival in the absence of apoptosis
Lum, J. J., Bauer, D. E., Kong, M., Harris, M. H., Li, C., Lindsten, T., & Thompson, C. B. (2005) · Cell · doi:10.1016/j.cell.2004.11.046 · Cited by 1,487 · see citing works
Self-citationGottlob, K., Majewski, N., Kennedy, S., Kandel, E., Robey, R. B., & Hay, N. (2001) · Genes & Development · doi:10.1101/gad.889901 · Cited by 961 · see citing works
VDAC2 Inhibits BAK Activation and Mitochondrial Apoptosis
Cheng, E. H.-Y., Sheiko, T. V., Fisher, J. K., Craigen, W. J., & Korsmeyer, S. J. (2003) · Science · doi:10.1126/science.1083995 · Cited by 852 · see citing works
Increased demand for NAD(+) relative to ATP drives aerobic glycolysis
Luengo, A., Li, Z., Gui, D. Y., Sullivan, L. B., Zagorulya, M., Do, B. T., Ferreira, R., Naamati, A., Ali, A., Lewis, C. A., et al. (2021) · Molecular Cell · doi:10.1016/j.molcel.2020.12.012 · Cited by 547 · see citing works
Growth factors can influence cell growth and survival through effects on glucose metabolism
Vander Heiden, M. G., Plas, D. R., Rathmell, J. C., Fox, C. J., Harris, M. H., & Thompson, C. B. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.17.5899-5912.2001 · Cited by 536 · see citing works
Self-citationRathmell, J. C., Heiden, M. G. V., Harris, M. H., Frauwirth, K. A., & Thompson, C. B. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)00066-6 · Cited by 467 · see citing works
Self-citationIL-7 Enhances the Survival and Maintains the Size of Naive T Cells
Rathmell, J. C., Farkash, E. A., Gao, W., & Thompson, C. B. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.12.6869 · Cited by 459 · see citing works
Self-citationAntimycin A mimics a cell-death-inducing Bcl-2 homology domain 3
Tzung, S.-P., Kim, K. M., Basañez, G., Giedt, C. D., Simon, J., Zimmerberg, J., Zhang, K. Y. J., & Hockenbery, D. M. (2001) · Nature Cell Biology · doi:10.1038/35055095 · Cited by 452 · see citing works
Vander Heiden, M. G., Li, X. X., Gottleib, E., Hill, R. B., Thompson, C. B., & Colombini, M. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m101590200 · Cited by 372 · see citing works
Self-citationJin, C., & Reed, J. C. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm832 · Cited by 340 · see citing works
Bonora, M., Wieckowski, M. R., Chinopoulos, C., Kepp, O., Kroemer, G., Galluzzi, L., & Pinton, P. (2015) · Oncogene · doi:10.1038/onc.2014.96 · Cited by 330 · see citing works
Mitochondria, oxygen free radicals, and apoptosis
Raha, S., & Robinson, B. H. (2001) · American Journal of Medical Genetics · doi:10.1002/ajmg.1398 · Cited by 306 · see citing works
Shi, Y., Chen, J., Weng, C., Chen, R., Zheng, Y., Chen, Q., & Tang, H. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(03)00871-4 · Cited by 158 · see citing works
Inhibition of Bak Activation by VDAC2 Is Dependent on the Bak Transmembrane Anchor
Lazarou, M., Stojanovski, D., Frazier, A. E., Kotevski, A., Dewson, G., Craigen, W. J., Kluck, R. M., Vaux, D. L., & Ryan, M. T. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.159301 · Cited by 111 · see citing works
Yip, K. W., Mao, X., Au, P. Y. B., Hedley, D. W., Chow, S., Dalili, S., Mocanu, J. D., Bastianutto, C., Schimmer, A., & Liu, F.-F. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-0536 · Cited by 99 · see citing works
Mitochondrial apoptosis without VDAC
Galluzzi, L., & Kroemer, G. (2007) · Nature Cell Biology · doi:10.1038/ncb0507-487 · Cited by 91 · see citing works
IMAI, H., KOUMURA, T., NAKAJIMA, R., NOMURA, K., & NAKAGAWA, Y. (2003) · Biochemical Journal · doi:10.1042/bj20021342 · Cited by 67 · see citing works
Initiation of Apoptotic Signal by the Peroxidation of Cardiolipin of Mitochondria
NAKAGAWA, Y. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1293.018 · Cited by 60 · see citing works
Transcription factor NF-kappa B represses ANT1 transcription and leads to mitochondrial dysfunctions
Zhang, C., Jiang, H., Wang, P., Liu, H., & Sun, X. (2017) · Scientific Reports · doi:10.1038/srep44708 · Cited by 37 · see citing works
- Authors
- Heiden, M. G. V., Chandel, N. S., Schumacker, P. T., & Thompson, C. B.
- Affiliations
- University of Chicago (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Thompson, Craig B
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 1999-02
- Volume
- 3
- Issue
- 2
- Pages
- 159-167
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2010953153
- Cited by
- 505
- References
- 35
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 5 · 2023: 6 · 2022: 10 · 2021: 8 · 2020: 11 · 2019: 4 · 2018: 11 · 2017: 10 · 2016: 10 · 2015: 10 · 2014: 19 · 2013: 11 · 2012: 10
- FWCI
- 19.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- 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 › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- Bcl-xL, growth factor withdrawal, apoptosis, adenine nucleotide translocase, voltage-dependent anion channel, mitochondrial membrane potential, cytochrome c release, oxidative phosphorylation, coupled respiration, metabolic arrest
- MeSH terms
- Adenosine Diphosphate, Sodium-Potassium-Exchanging ATPase, Adenosine Triphosphate, Animals, Biological Transport, Active, Fluorescent Dyes, Gramicidin, Hematopoietic Stem Cells, Interleukin-3, Membrane Potentials, Mitochondria, Oxidative Phosphorylation, Oxygen Consumption, Recombinant Fusion Proteins, Transfection, Tumor Cells, Cultured, Apoptosis, Porins, Proto-Oncogene Proteins c-bcl-2, Rhodamine 123, Voltage-Dependent Anion Channels, bcl-X Protein, Mice, Caspase Inhibitors
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