title: The Phospholipid:Diacylglycerol Acyltransferase Lro1 Is Responsible for Hepatitis C Virus Core-Induced Lipid Droplet Formation in a Yeast Model System.
abstract: Chronic infection with the hepatitis C virus frequently induces steatosis, which is a significant risk factor for liver pathogenesis. Steatosis is characterized by the accumulation of lipid droplets in hepatocytes. The structural protein core of the virus induces lipid droplet formation and localizes on the surface of the lipid droplets. However, the precise molecular mechanisms for the core-induced formation of lipid droplets remain elusive. Recently, we showed that the expression of the core protein in yeast as a model system could induce lipid droplet formation. In this study, we probed the cellular factors responsible for the formation of core-induced lipid-droplets in yeast cells. We demonstrated that one of the enzymes responsible for triglyceride synthesis, a phospholipid:diacylglycerol acyltransferase (Lro1), is required for the core-induced lipid droplet formation. While core proteins inhibit Lro1 degradation and alter Lro1 localization, the characteristic localization of Lro1 adjacent to the lipid droplets appeared to be responsible for the core-induced lipid droplet formation. RNA virus genomes have evolved using high mutation rates to maintain their ability to replicate. Our observations suggest a functional relationship between the core protein with hepatocytes and yeast cells. The possible interactions between core proteins and the endoplasmic reticulum membrane affect the mobilization of specific proteins.
authors.affiliation: Department of Microbiology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi, 981-8558, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Iwasa
authors.affiliation: Department of Microbiology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi, 981-8558, Japan.|Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, 980-8578, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Sato
authors.affiliation: Institute of Plant and Microbial Biology, Academia Sinica, Nangang, Taipei, 11529, Taiwan.
authors.forename: Chao-Wen
authors.initials: CW
authors.lastname: Wang
authors.affiliation: Institute of Plant and Microbial Biology, Academia Sinica, Nangang, Taipei, 11529, Taiwan.
authors.forename: Yun-Hsin
authors.initials: YH
authors.lastname: Cheng
authors.affiliation: Department of Microbiology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi, 981-8558, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Irokawa
authors.affiliation: Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, 980-8578, Japan.
authors.forename: Gi-Wook
authors.initials: GW
authors.lastname: Hwang
authors.affiliation: Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, 980-8578, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Naganuma
authors.affiliation: Department of Microbiology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi, 981-8558, Japan.
authors.forename: Shusuke
authors.initials: S
authors.lastname: Kuge
mesh_terms: D001692:Biological Transport; D051048:Diacylglycerol O-Acyltransferase / Q000235:genetics / Q000378:metabolism*; D060746:Endoplasmic Reticulum-Associated Degradation; D015870:Gene Expression; D016174:Hepacivirus / Q000502:physiology*; D066292:Lipid Droplets / Q000378:metabolism*; D050356:Lipid Metabolism; D010743:Phospholipids / Q000378:metabolism*; D059748:Proteolysis; D014758:Viral Core Proteins / Q000235:genetics / Q000378:metabolism*; D015003:Yeasts / Q000378:metabolism* / Q000821:virology*
chemical_list: D010743:Phospholipids; D014758:Viral Core Proteins; D051048:Diacylglycerol O-Acyltransferase