Figure 1.

In e-LLoC, LAMP2A participates in the loading of KFERQ-containing proteins into ILVs at the EE limiting membrane. HSPA8, CD63, PDCD6IP/ALIX, SDCBP/syntenin-1, RAB31 and the lipid ceramide participate in this mechanism as well. In contrast, e-Mi occurs in LE, is independent of LAMP2A and involves the ESCRT machinery (TSG101 and VSP4B), while CMA involves the translocation of substrates across the lysosomal membrane. It is possible that e-LLoC and e-Mi occur at different maturation stages of the endocytic pathway, e-LLoC at EE and e-Mi at LE (left panel). Alternatively, ESCRT and non-ESCRT machinery may be asymmetrically distributed (right panel). In this case, endosomes enriched in non-ESCRT machinery would be e-LLoC active, while endosomes enriched in ESCRT machinery would be e-Mi active. It is also possible that e-LLoC endosomes are more likely to fuse with the plasma membrane and release exosomes, while e-Mi endosomes are more prone to fuse with lysosomes for degradation.