Figure 1.

Types of autophagy in mammals and their anti- and pro-oncogenic roles. Macroautophagy, is a process of lysosomal degradation and recycling of cellular components, including damaged organelles, intracellular bacterial pathogens, and aggregated proteins. Macroautophagy sequesters cytosolic contents in de novo-generated double membrane vesicles called autophagosomes that finally fuse with lysosomes. Macroautophagy can be either in bulk or selective for a kind of cargo, and selectivity is mediated by selective autophagy receptors (SAR), or Hsc70 chaperone for protein aggregates in the case of Chaperone-Assisted Selective Autophagy (CASA). Selective macroautophagy binds cargo to the phagophore through lipidated LC3 proteins anchored to the latter’s membrane. Endosomal microautophagy, termed microautophagy in mammalian cells, caters on the degradation of cytosolic regions by late endosomes recognizing the substrates to be degraded, both by bulk degradation of proteins present in cytosol trapped in vesicles forming at the late endosome membrane, and by a selective degradation after binding to Hsc70 chaperone though KFERQ-like motifs. Latter are sorted into intraluminal vesicles in a manner dependent on the endosomal sorting complex required for transport III (ESCRT-III). CMA is a selective process of degradation of soluble, amenable to unfolding, cytosolic proteins presenting KFERQ-like motifs. The chaperone Hsc70 recognizes the motifs and transports the protein substrates to the lysosome where they bind to LAMP2A. LAMP2A multimerizes being stabilized by a glial fibrillary acidic protein (GFAP) and upon unfolding, the substrate is translocated through the lysosomal membrane with the assistance of a lysosomal resident Hsc70, and degraded in the lysosomal lumen. Both macroautophagy and CMA have anti- and pro-oncogenic roles, which depend on the cellular context and are summarized here.