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Autophagy in Premature Senescent Cells Is Activated via AMPK Pathway
Department of Biochemistry and Molecular Biology, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, China
Department of Gastroenterology, the First Affiliated Hospital of Nanchang University, Nanchang 330006, China
These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 7 February 2012; in revised form: 23 February 2012 / Accepted: 6 March 2012 / Published: 16 March 2012
Abstract: 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.
Keywords: autophagy; senescent cells; apoptosis; FoxO3A; AMPK; fibroblasts
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Cite This Article
MDPI and ACS Style
Guo, L.; Xie, B.; Mao, Z. Autophagy in Premature Senescent Cells Is Activated via AMPK Pathway. Int. J. Mol. Sci. 2012, 13, 3563-3582.
Guo L, Xie B, Mao Z. Autophagy in Premature Senescent Cells Is Activated via AMPK Pathway. International Journal of Molecular Sciences. 2012; 13(3):3563-3582.
Guo, Liujing; Xie, Bushan; Mao, Zebin. 2012. "Autophagy in Premature Senescent Cells Is Activated via AMPK Pathway." Int. J. Mol. Sci. 13, no. 3: 3563-3582.