Molecular Mechanism Of ACBD3 Regulating Autophagy

Autophagy is a highly conserved catabolic process induced under different conditions of cellular stress.Autophagy prevents cell damage and promotes survival when cells are in short of energy or nutrient or subjected to various cytotoxic insults.Thus,autophagy possesses primarily cytoprotective functions which are obtained through the long evolution and needs to be tightly regulated to respond correctly to the different stimuli that cells experience.A growing number of studies have shown that autophagical dysregulation is associated with a variety of diseases such as cancer,and neuronal disease.Many proteins and lipids are involved in the autophagy.Recent studies indicate that phosphatidylinositol-4-phosphate(PI4P)plays an important role in initiation and maturation of autophagosome.ACBD3 is a Golgi resident protein that plays many roles in a variety of physiological processes.Phosphatidylinositol 4-kinase IIIβ(PI4KIIIβ,or PI4KB)is a key enzyme in the Golgi complex,which is responsible for the synthesis of PI4 P.Importantly,ACBD3 recruits PI4 KB to the Golgi apparatus to produce PI4 P.Therefore,we propose that ACBD3 regulates autophagy through recruiting PI4 KB to the Golgi complex.In this paper,we aim to unveil the function of ACBD3 in autophagy,through measuring autophagic flow according to the expression levels of autophagy marker proteins LC3I/LC3 II and P62 in He La cells of ACBD3 knockdown or overexpression.The quantitative lipomics analysis showed that the total phosphatidylinositol content of ACBD3 knockdown cells was significantly reduced,compared with the control cells.However,the levels of the phosphatidylinositol with different chain length and different saturation decreased differently.We treated the He La cells starved for 1 hour and starved for 4 hours with PI4KB-specific inhibitor PIK93.The western blot results showed that the intensity of LC3 II bands increased in cells treated with PIK93,but the values of LC3 II/Actin did not change significantly,In addition,ATG5 and ATG7,two important players in autophagy,were significantly reduced,which implied that the decreased PI4 KB activity significantly inhibited autophagy.Therefore,we also believe that PI4 P generated by PI4 KB plays an important role in the process of autophagy.In summary,the Golgi resident protein ACBD3 plays an important role in the regulation of autophagy.Preliminary results indicate that ACBD3 regulates the process of autophagy by recruiting PI4 KB to reach the Golgi apparatus.Clearly,the molecular mechanisms underlying autophagy are complicated.We hope that by evaluating the important role of ACBD3 in the regulation of autophagy,we can further understand the molecular mechanism of autophagy and provide evidence for the diagnosis and treatment of related diseases.