Sterol homeostasis requires regulated degradation of squalene monooxygenase by the ubiquitin ligase Doa10/Teb4
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- dc.contributor.author Foresti, Ombrettaca
- dc.contributor.author Ruggiano, Annamaria, 1985-ca
- dc.contributor.author Hannibal-Bach, Hans K.ca
- dc.contributor.author Ejsing, Christer S.ca
- dc.contributor.author Carvalho, Pedro C.ca
- dc.date.accessioned 2014-06-06T10:04:33Z
- dc.date.available 2014-06-06T10:04:33Z
- dc.date.issued 2013ca
- dc.description.abstract Sterol homeostasis is essential for the function of cellular membranes and requires feedback inhibition of HMGR, a rate-limiting enzyme of the mevalonate pathway. As HMGR acts at the beginning of the pathway, its regulation affects the synthesis of sterols and of other essential mevalonate-derived metabolites, such as ubiquinone or dolichol. Here, we describe a novel, evolutionarily conserved feedback system operating at a sterol-specific step of the mevalonate pathway. This involves the sterol-dependent degradation of squalene monooxygenase mediated by the yeast Doa10 or mammalian Teb4, a ubiquitin ligase implicated in a branch of the endoplasmic reticulum (ER)-associated protein degradation (ERAD) pathway. Since the other branch of ERAD is required for HMGR regulation, our results reveal a fundamental role for ERAD in sterol homeostasis, with the two branches of this pathway acting together to control sterol biosynthesis at different levels and thereby allowing independent regulation of multiple products of the mevalonate pathway.
- dc.description.sponsorship Funding: Pedro Carvahlo: Center for Genomic Regulation (CRG), Spanish MCCIN, International Early Career Scientist. Howard Hughes Medical Institute; Christer S. Ejsing: Danish Council for Independent Research/Natural Sciences, Lundbeckfonden; Annamaria Ruggiano: La Caixa Graduate fellowship
- dc.format.mimetype application/pdfca
- dc.identifier.citation Foresti O, Ruggiano A, Hannibal-Bach HK, Ejsing CS, Carvalho P. Sterol homeostasis requires regulated degradation of squalene monooxygenase by the ubiquitin ligase Doa10/Teb4. eLife. 2013;2:e00953. DOI: 10.7554/eLife.00953ca
- dc.identifier.doi http://dx.doi.org/10.7554/eLife.00953
- dc.identifier.issn 2050-084Xca
- dc.identifier.uri http://hdl.handle.net/10230/22569
- dc.language.iso engca
- dc.publisher eLifeca
- dc.relation.ispartof eLife. 2013;2:e00953
- dc.rights © Foresti O, Ruggiano A, Hannibal-Bach HK, Ejsing CS, Carvalho P. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.ca
- dc.rights.accessRights info:eu-repo/semantics/openAccessca
- dc.rights.uri http://creativecommons.org/licenses/by/3.0/
- dc.subject.other Homeòstasi
- dc.subject.other Monooxigenases
- dc.subject.other Ubiqüitina
- dc.subject.other Enzims
- dc.title Sterol homeostasis requires regulated degradation of squalene monooxygenase by the ubiquitin ligase Doa10/Teb4ca
- dc.type info:eu-repo/semantics/articleca
- dc.type.version info:eu-repo/semantics/publishedVersionca