Growth factor regulation of autophagy and cell survival in the absence of apoptosis

摘要: In animals, cells are dependent on extracellular signals to prevent apoptosis. However, using growth factor-dependent from Bax/Bak-deficient mice, we demonstrate that apoptosis is not essential limit cell autonomous survival. Following factor withdrawal, Bax-/-Bak-/- activate autophagy, undergo progressive atrophy, and ultimately succumb death. These effects result loss of the ability take up sufficient nutrients maintain cellular bioenergetics. Despite abundant nutrients, factor-deprived ATP production catabolism intracellular substrates through autophagy. Autophagy for maintaining survival following withdrawal can sustain viability several weeks. During this time, respond readdition by rapid restoration metabolize glucose subsequent recovery their original size proliferative potential. Thus, signal transduction required direct utilization exogenous viability.