Inhibition of SCD1 impairs palmitate-derived autophagy at the step of autophagosome-lysosome fusion in pancreatic β-cells
Autophagy is indispensable for the proper architecture and flawless functioning of pancreatic β-cells. A growing body of evidence indicates reciprocal communication between autophagic pathways, apoptosis, and intracellular lipids. The way in which elevated levels of free saturated or unsaturated FAs...
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doaj-887b0013495349b493474a9c2f99e73e2021-04-29T04:34:30ZengElsevierJournal of Lipid Research0022-22752015-10-01561019011911Inhibition of SCD1 impairs palmitate-derived autophagy at the step of autophagosome-lysosome fusion in pancreatic β-cellsJustyna Janikiewicz0Katarzyna Hanzelka1Anna Dziewulska2Kamil Kozinski3Pawel Dobrzyn4Tytus Bernas5Agnieszka Dobrzyn6Laboratories of Cell Signaling and Metabolic Disorders, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, PolandLaboratories of Cell Signaling and Metabolic Disorders, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, PolandLaboratories of Cell Signaling and Metabolic Disorders, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, PolandLaboratories of Cell Signaling and Metabolic Disorders, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, PolandMedical Molecular Biochemistry, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, PolandFunctional and Structural Tissue Imaging, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, PolandLaboratories of Cell Signaling and Metabolic Disorders, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland; To whom correspondence should be addressed.Autophagy is indispensable for the proper architecture and flawless functioning of pancreatic β-cells. A growing body of evidence indicates reciprocal communication between autophagic pathways, apoptosis, and intracellular lipids. The way in which elevated levels of free saturated or unsaturated FAs contribute to progressive β-cell failure remains incompletely understood. Stearoyl-CoA desaturase (SCD)1, a key regulatory enzyme in biosynthesis of MUFAs, was shown to play an important role in regulation of β-cell function. Here, we investigated whether SCD1 activity is engaged in palmitate-induced pancreatic β-cell autophagy. We found augmented apoptosis and diminished autophagy upon cotreatment of INS-1E cells with palmitate and an SCD1 inhibitor. Furthermore, we found that additional treatment of the cells with monensin, an inhibitor of autophagy at the step of fusion, exacerbates palmitate-induced apoptosis. Accordingly, diminished SCD1 activity affected the accumulation, composition, and saturation status of cellular membrane phospholipids and neutral lipids. Such an effect was accompanied by aberrant endoplasmic reticulum stress, mitochondrial injury, and decreases in insulin secretion and cell proliferation. Our data reveal a novel mechanism by which the inhibition of SCD1 activity affects autophagosome-lysosome fusion because of perturbations in cellular membrane integrity, thus leading to an aberrant stress response and β-cell failure.http://www.sciencedirect.com/science/article/pii/S0022227520309664apoptosiscardiolipindiabetesfatty acid/desaturasesinsulinpancreas |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Justyna Janikiewicz Katarzyna Hanzelka Anna Dziewulska Kamil Kozinski Pawel Dobrzyn Tytus Bernas Agnieszka Dobrzyn |
spellingShingle |
Justyna Janikiewicz Katarzyna Hanzelka Anna Dziewulska Kamil Kozinski Pawel Dobrzyn Tytus Bernas Agnieszka Dobrzyn Inhibition of SCD1 impairs palmitate-derived autophagy at the step of autophagosome-lysosome fusion in pancreatic β-cells Journal of Lipid Research apoptosis cardiolipin diabetes fatty acid/desaturases insulin pancreas |
author_facet |
Justyna Janikiewicz Katarzyna Hanzelka Anna Dziewulska Kamil Kozinski Pawel Dobrzyn Tytus Bernas Agnieszka Dobrzyn |
author_sort |
Justyna Janikiewicz |
title |
Inhibition of SCD1 impairs palmitate-derived autophagy at the step of autophagosome-lysosome fusion in pancreatic β-cells |
title_short |
Inhibition of SCD1 impairs palmitate-derived autophagy at the step of autophagosome-lysosome fusion in pancreatic β-cells |
title_full |
Inhibition of SCD1 impairs palmitate-derived autophagy at the step of autophagosome-lysosome fusion in pancreatic β-cells |
title_fullStr |
Inhibition of SCD1 impairs palmitate-derived autophagy at the step of autophagosome-lysosome fusion in pancreatic β-cells |
title_full_unstemmed |
Inhibition of SCD1 impairs palmitate-derived autophagy at the step of autophagosome-lysosome fusion in pancreatic β-cells |
title_sort |
inhibition of scd1 impairs palmitate-derived autophagy at the step of autophagosome-lysosome fusion in pancreatic β-cells |
publisher |
Elsevier |
series |
Journal of Lipid Research |
issn |
0022-2275 |
publishDate |
2015-10-01 |
description |
Autophagy is indispensable for the proper architecture and flawless functioning of pancreatic β-cells. A growing body of evidence indicates reciprocal communication between autophagic pathways, apoptosis, and intracellular lipids. The way in which elevated levels of free saturated or unsaturated FAs contribute to progressive β-cell failure remains incompletely understood. Stearoyl-CoA desaturase (SCD)1, a key regulatory enzyme in biosynthesis of MUFAs, was shown to play an important role in regulation of β-cell function. Here, we investigated whether SCD1 activity is engaged in palmitate-induced pancreatic β-cell autophagy. We found augmented apoptosis and diminished autophagy upon cotreatment of INS-1E cells with palmitate and an SCD1 inhibitor. Furthermore, we found that additional treatment of the cells with monensin, an inhibitor of autophagy at the step of fusion, exacerbates palmitate-induced apoptosis. Accordingly, diminished SCD1 activity affected the accumulation, composition, and saturation status of cellular membrane phospholipids and neutral lipids. Such an effect was accompanied by aberrant endoplasmic reticulum stress, mitochondrial injury, and decreases in insulin secretion and cell proliferation. Our data reveal a novel mechanism by which the inhibition of SCD1 activity affects autophagosome-lysosome fusion because of perturbations in cellular membrane integrity, thus leading to an aberrant stress response and β-cell failure. |
topic |
apoptosis cardiolipin diabetes fatty acid/desaturases insulin pancreas |
url |
http://www.sciencedirect.com/science/article/pii/S0022227520309664 |
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