AMPK mediates a pro-survival autophagy downstream of PARP-1 activation in response to DNA alkylating agents
2013
Zhou, Jing | Ng, Shukie | Huang, Qing | Wu, You-Tong | Li, Zhengqiu | Yao, Shao Q. | Shen, Han-Ming
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.
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