PARP1 and Poly(ADP-ribosyl)ation Signaling during Autophagy in Response to Nutrient Deprivation

Figure 3

(a) PARylation regulates autophagy through AMPKα activation. PARP1 forms a complex with AMPKα in nucleus (1). During the starvation-induced autophagy, ROS production induces DNA damage and overactivation of PARP1. Auto-PARylated PARP1 is able to modify by PARylation in the AMPKα1 subunit (2). The complex is disrupted and PAR-AMPKα is exported to cytosol (3). The presence of PAR-AMPK and the continuous absence of amino acids and ATP depletion favor total activation of AMPKα population by LKB1, inhibition of mTORC1, interaction PAR-phospho-AMPK/ULK1, and autophagosome formation (4). LKB1 activity is presumably modified in a PARylation-dependent manner. (b) Starvation-induced ROS production was abrogated during the treatment with PARP inhibitors. Following AMPKα1/PARP1 interaction (1), the AMPKα1 subunit is not PARylated and the nuclear export of AMPK is inhibited (2 and 3). In spite of nutrient and energy depletion, AMPKα is inhibited; mTORC1 is partially activated and interacts with ULK1 favoring its inhibition (4). Finally, the autophagosomes production will be delayed.

(a)

(b)