Regulation Of Autophagy By DUB-X Via Destabilizing P62/SQSTM1

Autophagy is a process by which components of the cell are degraded to maintain essential activity and viability in response to nutrient limitation.Autophagy is important for maintaining normal living activities of the organism.Mitophagy is a selective form of autophagy by which dysfunctional mitochondria are degraded in autolysosomes,and mitophagy represents one type of mitochondrial quality control,which is essential for optimal mitochondrial bioenergetics.p62 is a protein encoded by the SQSTMI gene.As an important selective autophytic adapter protein,it plays a pivotal role in the selective autophagy of cells.Deubiquitination enzyme(DUB)is an important enzyme in the cell.It can remove the ubiquitin chain from the ubiquitinated protein,which affects the degradation and location of the protein in the cell and thus plays a very important role in the normal life activities of the cell.DUBs can also play an important role in the regulation of autophagy by regulating autophagy-related core factors such as ULK1.Recent studies have shown that p62 can be ubiquitinated.But it is still unclear whether DUBs can affect the process of autophagy by influencing the ubiquitination level of p62.Our study shows that there is a strong interaction between DUB-X and p62,and that the protein level of p62 is significantly increased after knockdown of DUB-X in a variety of cell lines.Further studies have shown that DUB-X can accelerate the degradation of p62.Our study indicated that DUB-X can regulate autophagy by influencing p62 protein levels by confocal microscopy and transmission electron microscopy.This study provides a new perspective for further understanding of how DUBs regulates autophagy.