Autophagy is activated, but is not required for the G₀ function of BCL-2 or BCL-xL

Abstract

Cell cycle arrest in G0 and autophagy have features in common, but the inter-relationship between the two processes is not well defined. The anti-apoptosis molecules BCL-2 and BCL-xL promote G0 arrest through upregulation of p27 protein, which can also induce autophagy. We tested the hypothesis that autophagy was involved in the cell cycle arrest function of BCL-2 and BCL-xL. We found that in IL-3-dependent FL5.12 cells, NIH3T3 cells, and mouse embryo fibroblasts induced to arrest, treatment with 3-methyladenine did not affect the expected decrease in cell size and ribosomal RNA synthesis, or upregulation of p27 levels. Using the m5-7 ATG5-/- MEF cell line with doxycycline-regulated ATG5 expression, we demonstrated that autophagy was activated during serum withdrawal and contact inhibition, but inhibition of autophagy had no measurable effect on G0 arrest in parental or BCL-xL-expressing cells. Thus, our data indicate that, in cell culture models, autophagy occurs but is not required for entrance into quiescence or for the G0 function of BCL-2 or BCL-xL.

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