br The role of p SQSTM in selective autophagy The
The role of p62/SQSTM1 in selective autophagy The most primitive and essential function of autophagy is to selectively degrade cytoplasmic components in the case of starvation and produce purchase atp gamma s and ATP to maintain the energy metabolism cycle of the body. With the deepening of the study it is found that autophagy can remove the misfolded proteins and damaged organelles selectively in the process of cell growth and metabolism, to maintain its steady state and normal physiological activities. Selective autophagy generally requires the presence of some adaptor proteins, such as p62 and NBR1, which have ubiquitin binding motif domain and LC3 interaction, and it can combine the ubiquitine-modified proteins, and transport to the autophagosome. As an important selective autophagy splice protein, p62 is served as a receptor in the removal of ubiquitinated proteins, and is also known as a selective autophagy receptor, which is the bridge binding LC3B to the ubiquitination substrate. It is generally accepted that the role of p62 during autophagy activation is to transmit the substrate to be degraded to the membrane surface LC3B. However, the current theory proves that p62 itself is one of the substrates to be biodegradable. With the participation of various Atg proteins, p62 and ubiquitinated protein are involved in the formation of autophagosome. The combination of p62 and upstream Atg protein is the initiation phase of autophagy, and then LC3B is recruited around this structure to form a phagocytic bubble. With the continuous extension of the bilayer membrane structure, the p62 protein, the substrate to be degraded, LC3B and other Atg proteins combine to form autophagosome, which is the necessary process of autophagy. The key step in the ultimate biological effect of autophagy is the integration of autophagosome with lysosome, which in turn forms autolysosome to degrade the contents of their encapsulation. This process is collectively referred to as autophagic flux. p62 protein level is usually negatively correlated with autophagic degradation. When autophagic flux is blocked, a large number of ubiquitinated proteins accumulate in the cells, the level of p62 protein will increase. While autophagic activity is enhanced, the level of p62 protein will decrease. p62 protein has now been recognized as a marker for assessing autophagy.
p62/SQSTM1 and atherosclerosis
Summary and outlook
Acknowledgments The research was supported by the National Natural Science Foundation of China (81672084).