Depletion of TM6SF2 disturbs membrane lipid composition and dynamics in HuH7 hepatoma cells |
| |
| Institution: | 1. Minerva Foundation Institute for Medical Research, Biomedicum 2U, FI-00290 Helsinki, Finland;2. Department of Biosciences, University of Helsinki, FI-00014 Helsinki, Finland;3. Biochemistry and Developmental Biology, Academic Medical Center Helsinki, Faculty of Medicine, University of Helsinki, FI-00014 Helsinki, Finland;4. Department of Anatomy, Academic Medical Center Helsinki, Faculty of Medicine, University of Helsinki, FI-00014 Helsinki, Finland;1. General Medicine and Metabolic Diseases, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, Italy;2. Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Ospedale Policlinico via F Sforza 35, 20122 Milano, Italy;3. Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milano, Italy;4. National Research Council (CNR), Institute of Clinical Physiology, Pisa, Italy;5. Translational Medicine, Department of Transfusion Medicine and Hematology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico Milano, Italy;6. Department of Surgery, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, Italy;7. Department of Pathology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, Italy;8. Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden;9. Cardiology Department, Sahlgrenska University Hospital, Gothenburg, Sweden;10. Clinical Nutrition Department of Medical and Surgical Science, University Magna Graecia, Catanzaro, Italy;11. Preclinical research center, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, Italy;12. Department of Medicine, Washington University School of Medicine, St. Louis, MO, Italy |
| |
| Abstract: | A polymorphism of TM6SF2 associates with hepatic lipid accumulation and reduction of triacylglycerol (TAG) secretion, but the function of the encoded protein has remained enigmatic. We studied the effect of stable TM6SF2 knock-down on the lipid content and composition, mitochondrial fatty acid oxidation and organelle structure of HuH7 hepatoma cells. Knock-down of TM6SF2 resulted in intracellular accumulation of TAGs, cholesterol esters, phosphatidylcholine (PC) and phosphatidylethanolamine. In all of these lipid classes, polyunsaturated lipid species were significantly reduced while saturated and monounsaturated species increased their proportions. The PCs encountered relative and absolute arachidonic acid (AA, 20:4n-6) depletion, and AA was also reduced in the total cellular fatty acid pool. Synthesis and turnover of the hepatocellular glycerolipids was enhanced. The TM6SF2 knock-down cells secreted lipoprotein-like particles with a smaller diameter than in the controls, and more lysosome/endosome structures appeared in the knock-down cells. The mitochondrial capacity for palmitate oxidation was significantly reduced. These observations provide novel clues to TM6SF2 function and raise altered mebrane lipid composition and dynamics among the mechanism(s) by which the protein deficiency disturbs hepatic TAG secretion. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
