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Addicted to Growth Factors?

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Science  31 Aug 2001:
Vol. 293, Issue 5535, pp. 1561
DOI: 10.1126/science.293.5535.1561b

Growth factors appear to limit apoptosis (programmed cell death) by changing the abundance or activity of proteins that control the apoptotic process. Now, Vander Heiden et al. propose another role for growth factors that can also influence apoptosis: control of nutrient uptake and bioenergetic homeostasis. In a mouse cell line that requires interleukin 3 (IL-3) for survival, after growth factor removal it was the level of reduction in glycolysis, not IL-3 concentration, that determined whether cells died. Cells used to high concentrations of IL-3, with higher glycolytic rates, were more susceptible to cell death due to growth factor withdrawal. When glucose was limited, mitochondria released cytochrome c and the cells underwent apoptosis. Sensitivity to decreases in nutrient availability was also greater in cells “addicted” to high levels of growth factor. Furthermore, overexpression of the glucose transporter Glut1, which would supply the cell with more nutrients, delayed apoptosis. Thus the effects of growth factors on the metabolic status of the cell are likely to be key factors determining whether it undergoes mitochondrial malfunction leading to apoptosis. — LBR

Mol. Cell. Biol.21, 5899 (2001).

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