Skip to main content
. Author manuscript; available in PMC: 2010 Jan 1.
Published in final edited form as: Immunol Rev. 2009 Jan;227(1):189–202. doi: 10.1111/j.1600-065X.2008.00725.x

Fig. 1. Autophagy pathway: signaling and execution stages of autophagy.

Fig. 1

The Tor signaling cascade controls autophagy execution. During starvation or other physiological conditions, Tor is inhibited. This is possibly dependent on the type III PI3K. When Tor is inhibited, Atg1 and hVPS34 complexed with Beclin 1 (Atg6) lead to activation of downstream Atg factors (Atg1) and set in motion the autophagy execution phases: 1. Initiation, formation of phagophore (isolation membrane). 2. Elongation, growth of the phagophore and its closure to generate a double membrane autophagosome. 3. Maturation of the double membrane autophagosomes into autolysosomes. The membrane elongation and shape are controlled by two protein (and lipid) conjugation systems, akin in activation and conjugation cascade principle to the ubiquitination system but distinct from it. Atg12 is initially conjugated to Atg7, which acts as an E1-activating enzyme, and then gets transferred to the E2-like conjugating enzyme Atg10. This intermediate presents Atg12 to be conjugated to a Lys residue in Atg5. Atg5 is essential for autophagy in the mouse. The Atg5–12 conjugate, stabilized in a noncovalent complex with Atg16, acts as an E3 enzyme for the second conjugation system, and triggers oligomerization on the outside membrane of the growing phagophore, and also enhances conversion of LC3-I (Atg8) into its C-terminally lipidated (with PE) form LC3-II. Upon autophagosome closure, sealing the typical double membrane organelle, Atg5–12/16 and LC3 (delipidated by Atg4) dissociate from the outer autophagosomal membrane and get recycled. The LC3 associated with the lumenal membrane remains trapped in the autophagosome and is degraded during maturation into the autolysosome, which involves fusion of autophagosomes with late endosomal (LE), multivesicular bodies endosomes (MVB) and lysosomal organelles (Lys), dissolution of internal membrane, and conversion of the maturing autophagic organelles into autolysosomes. hVPS34, interacting with UVRAG and HOPS, plays a role in maturation stages of autophagy. Depicted are autophagosomes capturing an intracellular organelle (mitochondria) or microbes such as intraphagosomal bacteria or bacteria released into the cytosol.