The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
The Proapoptotic Factors Bax and Bak Regulate T Cell Proliferation through Control of Endoplasmic Reticulum Ca2+ Homeostasis
Open accessAbstract
The Bcl-2-associated X protein (Bax) and Bcl-2-antagonist/killer (Bak) are essential regulators of lymphocyte apoptosis, but whether they play a role in viable T cell function remains unclear. Here, we report that T cells lacking both Bax and Bak display defects in antigen-specific proliferation because of Ca(2+)-signaling defects. Bax(-/-), Bak(-/-) T cells displayed defective T cell receptor (TCR)- and inositol-1,4,5-trisphosphate (IP(3))-dependent Ca(2+) mobilization because of altered endoplasmic reticulum (ER) Ca(2+) regulation that was reversed by Bax's reintroduction. The ability of TCR-dependent Ca(2+) signals to stimulate mitochondrial NADH production in excess of that utilized for ATP synthesis was dependent on Bax and Bak. Blunting of Ca(2+)-induced mitochondrial NADH elevation in the absence of Bax and Bak resulted in decreased reactive-oxygen-species production, which was required for T cell proliferation. Together, the data establish that Bax and Bak play an essential role in the control of T cell proliferation by modulating ER Ca(2+) release.
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“Restoring Ca2+ signals in Bax/Bak-null T cells restores mitochondrial ROS production and T cell proliferation (33).”
From Fueling Immunity: Insights into Metabolism and Lymphocyte Function (2013) · cites this paper as [33]
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“T cells lacking the apoptosis regulators Bax and Bak, which display defects in intracellular Ca2+ homeostasis, exhibit reduced Ca2+-dependent mitochondrial ROS production and T cell proliferation after TCR stimulation (33).”
From Fueling Immunity: Insights into Metabolism and Lymphocyte Function (2013) · cites this paper as [33]
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Cites
The versatility and universality of calcium signalling
Berridge, M. J., Lipp, P., & Bootman, M. D. (2000) · Nature Reviews Molecular Cell Biology · doi:10.1038/35036035 · Cited by 5,701
Self-citationProapoptotic 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
Self-citationThastrup, M., Cullen, P. J., Drøbak, B. K., Hanley, M. R., & Dawson, A. P. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.7.2466 · Cited by 3,272
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Lindsten, T., Ross, A. J., King, A., Zong, W.-X., Rathmell, J. C., Shiels, H. A., Ulrich, E., Waymire, K. G., Mahar, P., Frauwirth, K., et al. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)00136-2 · Cited by 1,489
Self-citationThe CD28 Signaling Pathway Regulates Glucose Metabolism
Frauwirth, K. A., Riley, J. L., Harris, M. H., Parry, R. V., Rathmell, J. C., Plas, D. R., Elstrom, R. L., June, C. H., & Thompson, C. B. (2002) · Immunity · doi:10.1016/s1074-7613(02)00323-0 · Cited by 1,475 · cited 2×
“TCR ligation activates pathways of cellular metabolism for energy production to meet the increased bioenergetic demands of cell growth and proliferation (Krauss et al., 2001; Frauwirth et al., 2002).”
BackgroundSelf-citationBAX and BAK Regulation of Endoplasmic Reticulum Ca 2+ : A Control Point for Apoptosis
Scorrano, L., Oakes, S. A., Opferman, J. T., Cheng, E. H. Y., Sorcinelli, M. D., Pozzan, T., & Korsmeyer, S. J. (2003) · Science · doi:10.1126/science.1081208 · Cited by 1,387
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
Self-citationMitochondria and calcium: from cell signalling to cell death
Duchen, M. R. (2000) · The Journal of Physiology · doi:10.1111/j.1469-7793.2000.00057.x · Cited by 1,261
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Cell death and endoplasmic reticulum stress: disease relevance and therapeutic opportunities
Kim, I., Xu, W., & Reed, J. C. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2755 · Cited by 1,840
Mitochondria as sensors and regulators of calcium signalling
Rizzuto, R., De Stefani, D., Raffaello, A., & Mammucari, C. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3412 · Cited by 1,781
Enhancing CD8 T-cell memory by modulating fatty acid metabolism
Pearce, E. L., Walsh, M. C., Cejas, P. J., Harms, G. M., Shen, H., Wang, L.-S., Jones, R. G., & Choi, Y. (2009) · Nature · doi:10.1038/nature08097 · Cited by 1,559
Self-citationFueling Immunity: Insights into Metabolism and Lymphocyte Function
Pearce, E. L., Poffenberger, M. C., Chang, C.-H., & Jones, R. G. (2013) · Science · doi:10.1126/science.1242454 · Cited by 1,363
Self-citationToll-like receptor–induced changes in glycolytic metabolism regulate dendritic cell activation
Krawczyk, C. M., Holowka, T., Sun, J., Blagih, J., Amiel, E., DeBerardinis, R. J., Cross, J. R., Jung, E., Thompson, C. B., Jones, R. G., et al. (2010) · Blood · doi:10.1182/blood-2009-10-249540 · Cited by 1,246
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Metadata
- Authors
- Jones, R. G., Bui, T., White, C., Madesh, M., Krawczyk, C. M., Lindsten, T., Hawkins, B. J., Kubek, S., Frauwirth, K. A., Wang, Y. L., Conway, S. J., Roderick, H. L., Bootman, M. D., Shen, H., Foskett, J. K., & Thompson, C. B.
- Affiliations
- University of Pennsylvania (US)
- University of Maryland, College Park (US)
- Cornell University (US)
- Babraham Institute (GB)
- Corresponding author
- Thompson, Craig B.
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2007-08
- Volume
- 27
- Issue
- 2
- Pages
- 268-280
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC2714273
- OpenAlex
- W2090734911
- Cited by
- 109
- References
- 46
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 3 · 2023: 3 · 2022: 2 · 2021: 3 · 2020: 3 · 2019: 5 · 2018: 5 · 2017: 1 · 2016: 2 · 2015: 5 · 2014: 7 · 2013: 12 · 2012: 11
- FWCI
- 4.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Open Research Online (The Open University) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Lirias (submittedVersion, other-oa)
- Funders
- Cancer Research Institute
- National Institutes of Health
- Biotechnology and Biological Sciences Research Council (BBS/E/B/0000C116, BBS/E/B/00001116, BBS/E/B/0000H110)
- National Cancer Institute (R01CA099179)
- National Institute of General Medical Sciences (R01GM056328)
- Abramson Family Cancer Research Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- Bax, Bak, Bcl-2 family proteins, T cell proliferation, endoplasmic reticulum calcium homeostasis, calcium signaling, T cell receptor signaling, inositol trisphosphate, mitochondrial NADH, reactive oxygen species, apoptosis, T cell function
- MeSH terms
- Adenosine Triphosphate, Animals, Calcium, Endoplasmic Reticulum, Energy Metabolism, Homeostasis, Mice, Mutant Strains, Mitochondria, NAD, Receptors, Antigen, T-Cell, T-Lymphocytes, Inositol 1,4,5-Trisphosphate, Apoptosis, Reactive Oxygen Species, Calcium Signaling, Cell Proliferation, bcl-2 Homologous Antagonist-Killer Protein, bcl-2-Associated X Protein, Mice
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