AMPK mediates a pro-survival autophagy downstream of PARP-1 activation in response to DNA alkylating agents

作者：Zhou Jing; Ng Shukie; Huang Qing; Wu You Tong; Li Zhengqiu; Yao Shao Q; Shen Han Ming^*

来源：FEBS LETTERS, 2013, 587(2): 170-177.

DOI：10.1016/j.febslet.2012.11.018

• Autophagy
• AMPK
• Alkylating agent
• DNA damage
• PARP-1
• Necrosis

In this study we aim to elucidate the signaling pathway and biological function of autophagy induced by MNNG, a commonly used DNA alkylating agent. We first observed that MNNG is able to induce necrotic cell death and autophagy in Bax-/- Bak-/- double knockout MEFs. We analyzed the critical role of PARP-1 activation and ATP depletion in MNNG-mediated cell death and autophagy via AMPK activation and mTOR suppression. We provide evidence that suppression of AMPK blocks MNNG-induced autophagy and enhances cell death, suggesting the pro-survival function of autophagy in MNNG-treated cells. Taken together, data from this study reveal a novel mechanism in controlling MNNG-mediated autophagy via AMPK activation downstream of PARP-1 activation and ATP depletion.

• 出版日期2013-1-16