Journal
AUTOPHAGY
Volume 5, Issue 2, Pages 273-276Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/auto.5.2.7640
Keywords
autophagy; AMPK; mTOR; ROS; PARP-1; necrosis; DNA damage
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Funding
- National Medical Research Council (NMRC)
- Biomedical Research Council (BMRC), Singapore
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Poly(ADP-ribose) polymerase-1 (PARP-1), activated by DNA strand breaks, participates in the DNA repair process physiologically. Excessive activation of PARP-1 mediates necrotic cell death under the status of oxidative stress and DNA damage. However, it remains elusive whether and how PARP-1 activation is involved in autophagy and what is the function of PARP-1-mediated autophagy under oxidative stress and DNA damage. We recently demonstrated that hydrogen peroxide (H2O2) induces autophagy through a novel autophagy signaling mechanism linking PARP-1 activation to the LKB1-AMP-activated protein kinase (AMPK)-mammalian target of rapamycin (mTOR) pathway. Furthermore, PARP-1-mediated autophagy plays a cytoprotective role in H2O2-induced necrotic cell death as suppression of autophagy greatly sensitizes H2O2-induced cell death. Our study thus identifies a novel function of PARP-1 in mediating autophagy and it appears that PARP-1 possesses a dual role in modulating necrosis and autophagy under oxidative stress and DNA damage: on the one hand, overactivation of PARP-1 leads to ATP depiction and necrotic cell death; on the other hand, PARP-1 activation promotes autophagy via the LKB1-AMPK-mTOR pathway to enhance cell survival. The cellular decision of life or death depends on the balance between autophagy and necrosis mediated by these two distinct pathways.
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