Autophagy in Premature Senescent Cells Is Activated via AMPK Pathway

作者：Guo, Liujing; Xie, Bushan; Mao, Zebin^*

来源：International Journal of Molecular Sciences, 2012, 13(3): 3563-3582.

DOI：10.3390/ijms13033563

• autophagy
• senescent cells
• apoptosis
• FoxO3A
• AMPK
• fibroblasts

Autophagy is a highly regulated intracellular process involved in the turnover of most cellular constituents and in the maintenance of cellular homeostasis. In this study, we show that the activity of autophagy increases in H2O2 or RasV12-induced senescent fibroblasts. Inhibiting autophagy promotes cell apoptosis in senescent cells, suggesting that autophagy activation plays a cytoprotective role. Furthermore, our data indicate that the increase of autophagy in senescent cells is linked to the activation of transcription factor FoxO3A, which blocks ATP generation by transcriptionally up-regulating the expression of PDK4, an inhibitor of pyruvate dehydrogenase complex, thus leading to AMPK activation and mTOR inhibition. These findings suggest a novel mechanism by which FoxO3A factors can activate autophagy via metabolic alteration.

• 出版日期2012-3
• 单位北京大学; 南昌大学