In the absence of extrinsic signals, nutrient utilization by lymphocytes is insufficient to maintain either cell size or viability
Open accessAbstract
Without receptor stimulation, cells from multicellular organisms die by apoptosis. Here we show that lymphocytes deprived of receptor stimulation undergo progressive atrophy before commitment to apoptosis. Following loss of receptor engagement, lymphocytes rapidly downregulated the glucose transporter, glut1. This was accompanied by reduction in mitochondrial potential and cellular ATP, suggesting that atrophy resulted from depletion of glucose-derived metabolic substrates. Expression of the antiapoptotic protein, Bcl-X(L), prevented death but not atrophy following either growth factor or glucose withdrawal. In Bcl-X(L) transgenic animals, size and metabolic activity of naive T cells were regulated through the TCR and correlated with TCR-dependent glut1 expression. These data suggest that ligands for cell-specific receptors promote cell survival by regulating nutrient uptake and utilization.
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Growth factor-deprived hematopoietic and neuronal cells fail to consume glucose in quantities sufficient to maintain cellular bioenergetics.
“when deprived of growth factors, hematopoietic and neuronal cells fail to consume glucose in quantities sufficient to even maintain cellular bioenergetics”
From The emerging hallmarks of cancer metabolism (2016) · cites this paper as Rathmell et al., 2000
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Self-citation
- Authors
- Rathmell, J. C., Heiden, M. G. V., Harris, M. H., Frauwirth, K. A., & Thompson, C. B.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Thompson, Craig B.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2000-09
- Volume
- 6
- Issue
- 3
- Pages
- 683-692
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2021597697
- Cited by
- 467
- References
- 44
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 15 · 2023: 17 · 2022: 20 · 2021: 25 · 2020: 16 · 2019: 19 · 2018: 36 · 2017: 22 · 2016: 21 · 2015: 15 · 2014: 13 · 2013: 17 · 2012: 23
- FWCI
- 6.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Pennsylvania
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- glucose transporter GLUT1, nutrient utilization, Bcl-xL, apoptosis, T cell receptor signaling, glucose deprivation, mitochondrial membrane potential, ATP depletion, naive T cells, cell survival, receptor engagement
- MeSH terms
- ATP Binding Cassette Transporter, Subfamily B, Member 2, Adenosine Triphosphate, Animals, Atrophy, Cell Division, Cell Survival, Cells, Cultured, Energy Metabolism, Female, Flow Cytometry, Glucose, Growth Substances, Interleukin-3, Ligands, Male, Mice, Inbred C57BL, Mice, Transgenic, Mitochondria, Monosaccharide Transport Proteins, Receptors, Antigen, T-Cell, T-Lymphocytes, Signal Transduction, Gene Expression, S Phase, Apoptosis, Homeodomain Proteins, ATP-Binding Cassette Transporters, Proto-Oncogene Proteins c-bcl-2, Cell Size, bcl-X Protein, Glucose Transporter Type 1, Mice
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