Cellular Senescence in Age-Related Macular Degeneration: Can Autophagy and DNA Damage Response Play a Role?

Figure 6

GATA4 can be involved in autophagy, senescence, and DNA damage response (DDR). The level of GATA4 is normally regulated by p62-dependent selective autophagy, but DNA damage and resulting DDR can release GATA4 from p62 control by its ATM-induced phosphorylation. If DNA damage cannot be repaired, DDR effectors induce permanent and irreversible cell cycle arrest, which is a hallmark of senescence with senescence-associated phenotype (SASP). GATA4 released from autophagic degradation can transactivate several genes that activate NF-κB, resulting in the release of growth factors, chemokines, cytokines, and other molecules typical for SASP.