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.