Which of the following best describes the role of LC3 in autophagy?
LC3 proteins are mammalian homologs of Saccharomyces Atg8, central ubiquitin like modifiers governing autophagosome membrane dynamics. Newly synthesized LC3 is cleaved by ATG4 family proteases exposing C terminal glycine to generate cytosolic LC3-I. Upon autophagy induction triggered by starvation or rapamycin, ATG7 E1 activates LC3-I, transfers to ATG3 E2, and ATG12 ATG5 ATG16L1 complex acting as E3 ligase conjugates LC3 to phosphatidylethanolamine on nascent isolation membrane, forming LC3-II. Lipidated LC3-II integrates into both inner and outer leaflets, promoting membrane hemifusion, elongation and closure, and providing docking platform via LIR motif for selective receptors p62, NBR1, NDP52 and optineurin linking ubiquitinated cargo. Because inner pool is degraded after autolysosome formation while outer pool recycled by ATG4 delipidation, presence of punctate LC3-II and conversion ratio LC3-II to LC3-I measured by western blot faithfully reports autophagosome number. LC3 does not act in ER associated degradation, chaperone assisted folding or SNARE recycling, which use distinct quality control machineries operating separately from autophagy.
Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 12: Autophagy and LC3 Lipidation Mechanism.