Regulation of membrane fluidity by RNF145-triggered degradation of the lipid hydrolase ADIPOR2
dc.contributor.author
Volkmar, Norbert
dc.contributor.author
Gawden-Bone, Christian M.
dc.contributor.author
Williamson, James C.
dc.contributor.author
Nixon-Abell, Jonathon
dc.contributor.author
West, James A.
dc.contributor.author
St George-Hyslop, Peter H.
dc.contributor.author
Kaser, Arthur
dc.contributor.author
Lehner, Paul J.
dc.date.accessioned
2022-10-05T08:04:11Z
dc.date.available
2022-08-26T03:56:41Z
dc.date.available
2022-08-29T08:47:00Z
dc.date.available
2022-10-05T08:04:11Z
dc.date.issued
2022-10-04
dc.identifier.issn
0261-4189
dc.identifier.issn
1460-2075
dc.identifier.other
10.15252/embj.2022110777
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/566560
dc.identifier.doi
10.3929/ethz-b-000566560
dc.description.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.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Wiley
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
adiponectin receptor 2
en_US
dc.subject
lipid homoestasis
en_US
dc.subject
membrane rigidity
en_US
dc.subject
palmitic acid
en_US
dc.subject
RNF145
en_US
dc.title
Regulation of membrane fluidity by RNF145-triggered degradation of the lipid hydrolase ADIPOR2
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
ethz.journal.title
The EMBO Journal
ethz.journal.volume
41
en_US
ethz.journal.issue
19
en_US
ethz.journal.abbreviated
EMBO J
ethz.pages.start
e110777
en_US
ethz.size
22 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
Hoboken, NJ
en_US
ethz.publication.status
published
en_US
ethz.date.deposited
2022-08-26T03:57:19Z
ethz.source
WOS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2022-10-05T08:04:12Z
ethz.rosetta.lastUpdated
2023-02-07T06:56:53Z
ethz.rosetta.versionExported
true
ethz.COinS
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Journal Article [133663]