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

Figure 2

Autophagy steps. (a) Membrane traffic associated to autophagosome formation. During autophagy, sequestration begins with the formation of a phagophore that expands into a double-membrane autophagosome. (1) Stages of nucleation and elongation: the autophagic charge will be engulfed by a double-lipid membrane called phagophore; the phagophore suffers elongation and closure to form an autophagosome. (2) This autophagosome may, or not, fuse with an endosome to form an amphisome. (3) Finally, the amphisome will fuse with lysosomes to form an autolysosome; in this step, acid hydrolases degrade the content of the autolysosome. Finally, the content may be recycled through permeases that efflux the content to the cytosol. (b) Vesicle induction and phagosome creation. In response to stress signals (starvation, hypoxia, and growth factor depletion), AMPk is activated and mTORC1 is inhibited, leading the stimulation of the ULK1 core (activation). ULK1 kinase will phosphorylate Beclin-1 leading to VPS34 activation and the initiation of phagophore formation (nucleation). ATG5-ATG12 conjugation involves ATG7 and ATG10 promoting an “E-like ligase” reaction of ATG12-ATG5-ATG16L influencing on the phospholipidic elongation of the double membranes. The complex ATG12-ATG5-ATG16L acts like an E3-function towards the LC3-PE assembly (LC3-II isoform) (elongation). Autophagosome maturations also involve fusion with lysosomes, degradation and recycling of nutrients and metabolites, and recycling of LC3-I isoform. This membrane trafficking maintains the same molecular events in nonselective and organelle-specific autophagy (mitophagy, ribophagy, and selective formation of amphisomes).

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