The effect of molecular chaperone mediated autophagy on ApoE expression in retinal pigment epithelial cells: Molecular structure and protein action mechanism

Int J Biol Macromol. 2024 Dec 22:139077. doi: 10.1016/j.ijbiomac.2024.139077. Online ahead of print.

Abstract

Chaperone mediated autophagy (CMA) represents a specialized mechanism of lysosomal protein breakdown, playing a crucial role as a metabolic pathway that helps to regulate and sustain cellular and systemic physiological equilibrium. Within the CMA process, proteins that contain sequences similar to KFERQ are specifically identified by the heat shock cognate protein 70. These proteins are then chaperoned to the lysosomes for subsequent degradation, a process facilitated by the lysosome associated membrane protein 2A. This particular research employed bioinformatics techniques to systematically screen for potential substrates of CMA. ApoE has a KFERQ like motif, which may be a substrate for CMA. Under conditions of starvation, hypoxia, H2O2, PA, and NaIO3, the expression of the rate limiting factor LAMP2A in CMA and ApoE increased significantly (P < 0.05). Under conditions of NaIO3, the expression of CMA related gene mRNA increased significantly (P < 0.05). When we use lysosomal blocker CQ to inhibit CMA activity, the expression level of ApoE in retinal pigment epithelial cells increased, and the difference was statistically significant (P < 0.05). When we inhibit CMA, the accumulation of ApoE in retinal pigment epithelial cells increases and cell viability decreases. When we activate CMA, the accumulation of ApoE decreases and cell viability increases. In retinal pigment epithelial cells, the drusen associated protein ApoE can be degraded through the CMA pathway.

Keywords: Age related macular degeneration; ApoE; LAMP2A; Molecular chaperone autophagy.