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  • Title: AMPK mediates a pro-survival autophagy downstream of PARP-1 activation in response to DNA alkylating agents.
    Author: Zhou J, Ng S, Huang Q, Wu YT, Li Z, Yao SQ, Shen HM.
    Journal: FEBS Lett; 2013 Jan 16; 587(2):170-7. PubMed ID: 23201261.
    Abstract:
    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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