Quantitative Lipidomics Reveals Function Of ACBD3 In Lipid Metabolism In Mammalian Cells

Like Proteins and Nucleic acids,Lipids perform important functions in mammalian Cells as well.For a long time,research interests of scientists focus on structure and function of Proteins and Nucleic acids.Unfortunately,Lipids have been ignored.With the increasing understanding of the biological function of Lipids and improvement of research methods,such as newly developed lipidomics,the phenomena has been changed greatly.Recently,scientists found that Lipids play important roles in Cell signaling,Cell polarity establishment and maintenance,Cell migration and Cell homeostasis.The advance in the research fields relevant to Lipids inspire people to study Lipids metabolism in Cells.In addition,with the progress of lipidomics analysis technologies and the improvement of profiling,identification and quantitative analysis of Lipids,systematic study on structure and function of Lipids goes into a novel era.Lipid biosynthesis mostly starts in Endoplasmic Reticulum(ER)in mammalian Cells.It then be transported to the Golgi apparatus,further processed and modified here,and finally delivered to specific spot in the Cell or on the Cell surface to execute its function.Thus,the integrity of the Golgi complex is important for Lipids metabolism.Golgi protein ACBD3 is a member of ACBDs family,which contains Acyl-CoA binding domain with potential ability to bind Acyl-CoA.Due to important roles of Acyl CoA in the metabolism of Sphingolipids,Glycolipids and other lipids,we will apply lipidomics methodology to study the function of ACBD3 in Lipid metabolism in this project.We found that the Golgi complex was fragmented when ACBD3 expression was knockdown through transfecting siRNA into HeLa Cell,which strongly support that ACBD3 plays an important role in maintaining Golgi structure.Next,lipidomics analysis indicated that ACBD3 knockdown changed the levels of PS,GlcCer,PI and LPE significantly.In ACBD3 knockdown Cells,the levels of PS and GluCer were increased,while the levels of PI and LPE were cut down.Our statistics analysis showed that ACBD3 knockdown increased the levels of the Lipid molecule with more double bonds and longer carbon chain in one Lipid species.In the further rescue experiment,when we express GFP-ACBD3 in its knockdown Cells,we found the impaired Golgi complex and abnormal lipid metabolism coursed by ACBD3 knockdown can be rescued partially.Together results suggest that ACBD3 is vital to Golgi morphology and functions in lipid metabolism.Taken together,we applied quantitative lipidomics to study the function of ACBD3 in Lipid metabolism systematically and got a preliminary insight into molecular mechanism of ACBD3 regulating Lipid metabolism.Interactions between molecules within cell are involved in almost every cellular physiological process,and become the molecular mechanisms underlying the basic cellular activities.Therefore,we will combine lipidomics and molecular Cell biology to explore the detailed molecular mechanism of ACBD3 regulating Lipid metabolism through building ACBD3-centered molecular interacting network.