Cell Survival

Survival of the Fattest

Science's STKE  03 Oct 2000:
Vol. 2000, Issue 52, pp. tw1
DOI: 10.1126/stke.2000.52.tw1

Even after they have finished proliferating, many mature cells require continued stimulation by growth factors to prevent apoptosis. However, it has not been elucidated what biochemical mechanism leads to cell death in such instances. Stimulation by growth factors could conceivably block one or more events in a constitutive death pathway, or it might simply keep cellular metabolism stimulated to a level that supports cell survival. Rathmell et al. studied the stimulatory requirements of a lymphoid cell line that requires interleukin 3 (IL-3) for survival and primary T cells that require stimulation of antigen receptors by major histocompatibility complex (MHC) proteins. They found that survival factors actually appear to function by altering basic cellular physiology, in particular, nutrient uptake. Without receptor stimulation, cells lost expression of the glucose transporter Glut1 and showed decreased mitochondrial function. If glucose was depleted from the culture medium, survival factors no longer prevented cell death. On the other hand, survival promoted by the anti-apoptotic protein Bcl-XL allowed cells to survive without growth factors regardless of nutrient content in the culture medium but did not prevent the decreased energy production associated with growth factor withdrawal. The results indicate that mature, unstimulated lymphocytes do not inherently achieve metabolic homeostasis, but rather function under dynamic regulation by extracellular signals.

Rathmell, J.C., Vander Heiden, M.G., Harris, M.H., Frauwirth, K.A., and Thompson, C.B. (2000) In the absence of extrinsic signals, nutrient utilization by lymphocytes is insufficient to maintain either cell size or viability. Mol. Cell 6: 683-692. [Online Journal]