Differentially localized acyl-CoA synthetase 4 isoenzymes mediate the metabolic channeling of fatty acids towards phosphatidylinositol

• Verfasst von: Küch, Eva-Maria [VerfasserIn]
• Verfasst von: Vellaramkalayil, Regina [VerfasserIn]
• Verfasst von: Zhang, Ingrid [VerfasserIn]
• Verfasst von: Lehnen, Daniela [VerfasserIn]
• Verfasst von: Brügger, Britta [VerfasserIn]
• Verfasst von: Stremmel, Wolfgang [VerfasserIn]
• Verfasst von: Ehehalt, Robert [VerfasserIn]
• Verfasst von: Poppelreuther, Margarete [VerfasserIn]
• Verfasst von: Füllekrug, Joachim [VerfasserIn]
• Titel: Differentially localized acyl-CoA synthetase 4 isoenzymes mediate the metabolic channeling of fatty acids towards phosphatidylinositol
• Verf.angabe: Eva-Maria Küch, Regina Vellaramkalayil, Ingrid Zhang, Daniela Lehnen, Britta Brügger, Wolfgang Stremmel, Robert Ehehalt, Margarete Poppelreuther, Joachim Füllekrug
• Jahr: 2014
• Umfang: 13 S.
• Fussnoten: Gesehen am 22.06.2021 ; Available online 5 November 2013
• Titel Quelle: In: Biochimica et biophysica acta. Molecular and cell biology of lipids
• Ort Quelle: Amsterdam : Elsevier, 1998
• Jahr Quelle: 2014
• Band/Heft Quelle: 1841(2014), 2, Seite 227-239
• ISSN Quelle: 1879-2618
• DOI: doi:10.1016/j.bbalip.2013.10.018
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: ACSL4
• Sach-SW: Acyl-CoA synthetase
• Sach-SW: Fatty acid uptake
• Sach-SW: Localization
• Sach-SW: Phosphatidylinositol
• K10plus-PPN: 1503212653

Abstract

The acyl-CoA synthetase 4 (ACSL4) has been implicated in carcinogenesis and neuronal development. Acyl-CoA synthetases are essential enzymes of lipid metabolism, and ACSL4 is distinguished by its preference for arachidonic acid. Two human ACSL4 isoforms arising from differential splicing were analyzed by ectopic expression in COS cells. We found that the ACSL4_v1 variant localized to the inner side of the plasma membrane including microvilli, and was also present in the cytosol. ACSL4_v2 contains an additional N-terminal hydrophobic region; this isoform was located at the endoplasmic reticulum and on lipid droplets. A third isoform was designed de novo by appending a mitochondrial targeting signal. All three ACSL4 variants showed the same specific enzyme activity. Overexpression of the isoenzymes increased cellular uptake of arachidonate to the same degree, indicating that the metabolic trapping of fatty acids is independent of the subcellular localization. Remarkably, phospholipid metabolism was changed by ACSL4 expression. Labeling with arachidonate showed that the amount of newly synthesized phosphatidylinositol was increased by all three ACSL4 isoenzymes but not by ACSL1. This was dependent on the expression level and the localization of the ACSL4 isoform. We conclude that in our model system exogenous fatty acids are channeled preferentially towards phosphatidylinositol by ACSL4 overexpression. The differential localization of the endogenous isoenzymes may provide compartment specific precursors of this anionic phospholipid important for many signaling processes.