The fatty acid 2-hydroxylase (FA2H) is essential for synthesis of 2-hydroxylated fatty acids in myelinating and other cells, and deficiency of this enzyme causes a complicated form of hereditary spastic paraplegia also known as fatty acid hydroxylase-associated neurodegeneration. Despite its important role in sphingolipid metabolism, regulation of FA2H and its interaction with other proteins involved in the same or other metabolic pathways is poorly understood. To identify potential interaction partners of the enzyme, quantitative mass spectrometry using stable isotope labeling of cells was combined with formaldehyde cross-linking and proximity biotinylation, respectively. Besides other enzymes involved in sphingolipid synthesis and intermembrane transfer of ceramide, and putative redox partners of FA2H, progesterone receptor membrane component-1 (PGRMC1) and PGRMC2 were identified as putative interaction partners. These two related heme-binding proteins are known to regulate several cytochrome P450 enzymes. Bimolecular fluorescence complementation experiments confirmed the interaction of FA2H with PGRMC1. Moreover, the PGRMC1 inhibitor AG-205 significantly reduced synthesis of hydroxylated ceramide and glucosylceramide in FA2H-expressing cells. This suggests that PGRMC1 may regulate FA2H activity, possibly through its heme chaperone activity.
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March 2018
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The human immunodeficiency virus. In this issue of the Biochemical Journal, Parajuli et al. report that restricted the HIV Env (envelope glycoprotein) glycan engagement by a lectin reengineered DAVEI protein chimera is sufficient for virolysis. For details, see pages 931–957.
Research Article|
March 06 2018
Identification of progesterone receptor membrane component-1 as an interaction partner and possible regulator of fatty acid 2-hydroxylase
Robert Hardt;
Robert Hardt
1Institute of Biochemistry and Molecular Biology, University of Bonn, Nussallee 11, 53115 Bonn, Germany
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Dominic Winter;
Dominic Winter
1Institute of Biochemistry and Molecular Biology, University of Bonn, Nussallee 11, 53115 Bonn, Germany
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Volkmar Gieselmann;
Volkmar Gieselmann
1Institute of Biochemistry and Molecular Biology, University of Bonn, Nussallee 11, 53115 Bonn, Germany
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Matthias Eckhardt
1Institute of Biochemistry and Molecular Biology, University of Bonn, Nussallee 11, 53115 Bonn, Germany
Correspondence: Matthias Eckhardt ([email protected])
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Publisher: Portland Press Ltd
Received:
December 20 2017
Revision Received:
February 02 2018
Accepted:
February 08 2018
Accepted Manuscript online:
February 09 2018
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2018
Biochem J (2018) 475 (5): 853–871.
Article history
Received:
December 20 2017
Revision Received:
February 02 2018
Accepted:
February 08 2018
Accepted Manuscript online:
February 09 2018
Citation
Robert Hardt, Dominic Winter, Volkmar Gieselmann, Matthias Eckhardt; Identification of progesterone receptor membrane component-1 as an interaction partner and possible regulator of fatty acid 2-hydroxylase. Biochem J 15 March 2018; 475 (5): 853–871. doi: https://doi.org/10.1042/BCJ20170963
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