Depletion of TM6SF2 disturbs membrane lipid composition and dynamics in HuH7 hepatoma cells.

Research output: Contribution to journalArticleScientificpeer-review

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.
Original languageEnglish
JournalBiochimica and Biophysica Acta. Molecular and Cell Biology of Lipids
Volume1862
Issue number7
Pages (from-to)676-685
Number of pages10
ISSN1388-1981
DOIs
Publication statusPublished - May 2017
MoE publication typeA1 Journal article-refereed

Fields of Science

  • 1184 Genetics, developmental biology, physiology
  • 1182 Biochemistry, cell and molecular biology

Cite this

@article{40663c7cf358419c9ac70860e21b6ef1,
title = "Depletion of TM6SF2 disturbs membrane lipid composition and dynamics in HuH7 hepatoma cells.",
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 theprotein deficiency disturbs hepatic TAG secretion.",
keywords = "1184 Genetics, developmental biology, physiology, 1182 Biochemistry, cell and molecular biology",
author = "Hanna Ruhanen and Haridas, {P.A. Nidhina} and Eeva-Liisa Eskelinen and Ove Eriksson and Olkkonen, {Vesa M.} and Reijo K{\"a}kel{\"a}",
year = "2017",
month = "5",
doi = "10.1016/j.bbalip.2017.04.004",
language = "English",
volume = "1862",
pages = "676--685",
journal = "Biochimica and Biophysica Acta. Molecular and Cell Biology of Lipids",
issn = "1388-1981",
publisher = "Elsevier Scientific Publ. Co",
number = "7",

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TY - JOUR

T1 - Depletion of TM6SF2 disturbs membrane lipid composition and dynamics in HuH7 hepatoma cells.

AU - Ruhanen, Hanna

AU - Haridas, P.A. Nidhina

AU - Eskelinen, Eeva-Liisa

AU - Eriksson, Ove

AU - Olkkonen, Vesa M.

AU - Käkelä, Reijo

PY - 2017/5

Y1 - 2017/5

N2 - 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 theprotein deficiency disturbs hepatic TAG secretion.

AB - 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 theprotein deficiency disturbs hepatic TAG secretion.

KW - 1184 Genetics, developmental biology, physiology

KW - 1182 Biochemistry, cell and molecular biology

UR - http://dx.doi.org/10.1016/j.bbalip.2017.04.004

U2 - 10.1016/j.bbalip.2017.04.004

DO - 10.1016/j.bbalip.2017.04.004

M3 - Article

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SP - 676

EP - 685

JO - Biochimica and Biophysica Acta. Molecular and Cell Biology of Lipids

JF - Biochimica and Biophysica Acta. Molecular and Cell Biology of Lipids

SN - 1388-1981

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ER -