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. Author manuscript; available in PMC: 2017 Mar 1.
Published in final edited form as: Exp Eye Res. 2015 Aug 28;144:46–53. doi: 10.1016/j.exer.2015.08.018

Figure 4. Multifunctional p62 in the regulation of proteolysis.

Figure 4

RPE cells in the macula are constantly exposed to the daily heterophagy. The capacity to defend against oxidative stress decreases in aged RPE cells. The simultaneous oxidative stress and impaired defense systems damage cellular proteins and evoke detrimental protein aggregation. Prior to aggregation, heat-shock proteins (Hsps) attempt to refold misfolded proteins. Once Hsp repair capacity is exceeded, individual polypeptides can be degraded by the ubiquitin (Ub) targeted proteasome, while aggregates are degraded by autophagy. p62 sorts proteins between proteasomal and autophagic clearance pathways. It binds to Ub cargoes and to LC3. p62 interacts with the Nrf2/ARE by disrupting the cytoplasmic Nrf2-Keap1 complex and thereby regulates antioxidant production. A functional ARE element is located in the regulatory region of the p62 gene.