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International journal of molecular sciences 2012, PMID: 22489168

Autophagy in Premature Senescent Cells Is Activated via AMPK Pathway.

Guo, Liujing; Xie, Bushan; Mao, Zebin

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 H(2)O(2) 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.

Document information provided by NCBI PubMed

Text Mining Data

pyruvate dehydrogenase complex ⊣ PDK4: " 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 "

mTOR ⊣ AMPK: " 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 "

Manually curated Databases

No curated data.