Figure legends
Figure 1: Mechanisms of extracellular complement-mediated autophagy induction via surface receptors and MAC. For details, see text.
Figure 2: Potential mechanisms of intracellular C3 involvement in autophagy: (1) C3-coated bacteria have been shown to be targeted by autophagy through interaction with ATG16L1, leading to bacterial growth restriction. Similarly, intracellular C3 deposited on organelles could recruit the ATG16L1-ATG12-ATG5 complex that catalyzes the lipidation of LC3-I to LC3-II, driving the formation of autophagosomes. (2) C3 may deliver small portions of material for expansion of the autophagosome membrane. This may involve C3 activity upstream or downstream of ATG16L1. (3) Processing of C3 could liberate ATG16L1 complex from the autophagosomal membrane, allowing fusion of completed autophagosomes with lysosomes. (4) Cleaved forms of C3 anchored in the membrane of autophagosomes could facilitate autophagosome-lysosome fusion via interactions with yet unknown factors. These mechanisms are not mutually exclusive.
Figure 3: A scheme for the potential C3 binding domain on ATG16L1, based on experimental evidence. The recombinant proteins found on protein microarrays and the construct used in yeast 2-hybrid assay suggests that C3 binds to the coiled coil domain of ATG16L1, which is responsible for ATG16L1 recruitment to the phagophore membrane during homeostatic autophagy. ATG5BD: ATG5 binding domain.