The Macroautophagy Machinery in Endo- and Exocytosis

Macroautophagy and the autophagy-related gene (Atg) machinery execute during their canonical function cytoplasmic constituent degradation in lysosomes. This canonical function contributes to pathogen restriction and intracellular antigen presentation on major histocompatibility complex (MHC) class II molecules to CD4⁺ T cells. However, in the recent years, it has become clear that the Atg machinery is also used for other membrane transport functions, including endocytosis and exocytosis. This review describes these non-canonical functions in the context of antigen presentation on MHC class I and II molecules to CD8⁺ and CD4⁺ T cells, respectively, and during viral replication. Future studies will need to address how the Atg machinery is modified for these non-canonical functions, gets recruited to the respective sites of membrane modification, and recruits alternative Atg interactors to execute endo- and exocytosis instead of macroautophagy.