The Function Of PIP5KI Family In The Process Of Autophagy

Autophagy is one of the conserved degradative pathways in Eukaryotes which islysosome-dependent. During autophagy, the double memberane structure which isnamed autophagosomes engulf and deliver the damaged organelles and aggregatedproteins to lysosomes for degradation.In the initiation of autophagy process, the pre-autophagosome, named omegasome,will establish on the ER. Some autophagy related proteins then will be recruited toomegasome and form the autophagosome which will separate from omegasome finally.In our study, we found that type Iphosphatidylinositol4-phosphate5-kinase isoformC(PIP5KIC) is involved in the formation of autophagosome. In mammalian cells, whenPIP5KIC is knocked down, we observed that omegasome morphology is abnormal andautophagy level also decreases. And in yeast cells we found the similar phenotype.Deletion of Mss4,which is the homologue of PIP5KI in yeast, led to the reduction ofboth autophagy level and autophagosome formation. According to these evidences, weconcluded that type I phosphatidylinositol4-phosphate5-kinase plays an important rolein autophagosome formation.In the late stage, autolysosome will produce pre-lysosome in a tubulation way andthis process is named autophagic lysosomal reformation (ALR). In our study, we foundthat the other two members of type Iphosphatidylinositol4-phosphate5-kinase werealso involved in ALR process and the two isoforms played different roles in ALR.During ALR, PIP5KIB, which was partially located in autolysosome, firstly turned PI4Pto PIP2, and then PIP2recruited Clathrin and its adaptor protein to form curvature onthe autolysosome membrane and start the ALR process. After tubulation by motorproteins, PIP5KIA turned PI4P into PIP2in the autolysosome tube. The local PIP2willalso recruit Clathrin and the adaptor protein for the fission of tubules to produce thepre-lysosome.