Figure 5.

Cellular and extracellular waste clearing. Cellular waste, including misfolded, aggregated and damaged proteins as well as damaged organelles (presented as small ovals or squares of different colors) is subjected by two main machineries: ubiquitin-proteasome system (UPS) and autophagy, which can be in the form of macroautophagy, including mitophagy, microautophagy and chaperone-mediated autophagy (CMA). Unfolded proteins are a substrate for unfolded protein response (UPR, not represented here), which directs them to degradation either by autophagy or UPS. Heterophagy, which degrades extracellular debris inside the cell, is of a particular importance in retinal pigment epithelium cells and is usually carried out by endocytosis. Exosomes can transport waste material out of the cell. LAMP-2A—lysosomal associated membrane protein 2A. The black arrows indicate the sequence of events.