Regulation of membrane fluidity by RNF145 ‐triggered degradation of the lipid hydrolase ADIPOR2
Abstract: The regulation of membrane lipid composition is critical for cellular homeostasis. Cells are particularly sensitive to phospholipid saturation, with increased saturation causing membrane rigidification and lipotoxicity. How mammalian cells sense membrane lipid composition and reverse fatty acid (FA)‐induced membrane rigidification is poorly understood. Here we systematically identify proteins that differ between mammalian cells fed saturated versus unsaturated FAs. The most differentially expressed proteins were two ER‐resident polytopic membrane proteins: the E3 ubiquitin ligase RNF145 and the lipid hydrolase ADIPOR2. In unsaturated lipid membranes, RNF145 is stable, promoting its lipid‐sensitive interaction, ubiquitination and degradation of ADIPOR2. When membranes become enriched in saturated FAs, RNF145 is rapidly auto‐ubiquitinated and degraded, stabilising ADIPOR2, whose hydrolase activity restores lipid homeostasis and prevents lipotoxicity. We therefore identify RNF145 as a FA‐responsive ubiquitin ligase which, together with ADIPOR2, defines an autoregulatory pathway that controls cellular membrane lipid homeostasis and prevents acute lipotoxic stress.
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Erschienen in
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Regulation of membrane fluidity by RNF145 ‐triggered degradation of the lipid hydrolase ADIPOR2 ; day:22 ; month:08 ; year:2022 ; extent:22
The EMBO journal / European Molecular Biology Organization ; (22.08.2022) (gesamt 22)
- Urheber
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Volkmar, Norbert
Gawden‐Bone, Christian M.
Williamson, James C.
Nixon‐Abell, Jonathon
West, James A.
St George‐Hyslop, Peter H.
Kaser, Arthur
Lehner, Paul J.
- DOI
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10.15252/embj.2022110777
- URN
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urn:nbn:de:101:1-2022082215332210888470
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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15.08.2025, 07:22 MESZ
Datenpartner
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Beteiligte
- Volkmar, Norbert
- Gawden‐Bone, Christian M.
- Williamson, James C.
- Nixon‐Abell, Jonathon
- West, James A.
- St George‐Hyslop, Peter H.
- Kaser, Arthur
- Lehner, Paul J.
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