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PMID: 11030347 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

In the absence of extrinsic signals, nutrient utilization by lymphocytes is insufficient to maintain either cell size or viability.

Molecular cell ·Vol. 6 ·No. 3 ·2000-09-00 ·Pages 683-92

Rathmell JC, Vander Heiden MG, Harris MH, Frauwirth KA, Thompson CB

Abstract

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.

MeSH Terms

ATP Binding Cassette Transporter, Subfamily B, Member 2 ATP-Binding Cassette Transporters/genetics Adenosine Triphosphate/metabolism Animals Apoptosis/physiology Atrophy Cell Division/drug effects,physiology Cell Size/physiology Cell Survival/drug effects,physiology Cells, Cultured Energy Metabolism/physiology Female Flow Cytometry Gene Expression/drug effects,physiology Glucose/pharmacokinetics Glucose Transporter Type 1 Growth Substances/pharmacology Homeodomain Proteins/genetics Interleukin-3/pharmacology Ligands Male Mice Mice, Inbred C57BL Mice, Transgenic Mitochondria/metabolism Monosaccharide Transport Proteins/genetics,metabolism Proto-Oncogene Proteins c-bcl-2/genetics Receptors, Antigen, T-Cell/physiology S Phase/physiology Signal Transduction/physiology T-Lymphocytes/cytology,metabolism bcl-X Protein

Chemicals

ATP Binding Cassette Transporter, Subfamily B, Member 2 ATP-Binding Cassette Transporters Bcl2l1 protein, mouse Glucose Transporter Type 1 Growth Substances Homeodomain Proteins Interleukin-3 Ligands Monosaccharide Transport Proteins Proto-Oncogene Proteins c-bcl-2 Receptors, Antigen, T-Cell Slc2a1 protein, mouse TAP1 protein, human Tap1 protein, mouse bcl-X Protein RAG-1 protein Adenosine Triphosphate Glucose

Authors & Affiliations

5 authors, click to expand affiliations / ORCID

Rathmell J C

Department of Cancer Biology and Medicine and Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia 19104, USA.

Vander Heiden M G

Harris M H

Frauwirth K A

Thompson C B

Article Info

Journal

Molecular cell

Abbr.

Mol Cell

ISSN

1097-2765

DOI

10.1016/s1097-2765(00)00066-6

Published

2000-09-00

Pages

683-92

Language

English

Region

United States

NLM ID

9802571

Subset

External Links

PubMed source DOI: 10.1016/s1097-2765(00)00066-6 View journal details

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In the absence of extrinsic signals, nutrient utilization by lymphocytes is insufficient to maintain either cell size or viability.

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