Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Diacylglycerol triggers Rim101 pathway-dependent necrosis in yeast: a model for lipotoxicity
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. NAWI Graz, Austria; University of Graz, Austria.
Show others and affiliations
Number of Authors: 222018 (English)In: Cell Death and Differentiation, ISSN 1350-9047, E-ISSN 1476-5403, Vol. 25, no 4, p. 765-781Article in journal (Refereed) Published
Abstract [en]

The loss of lipid homeostasis can lead to lipid overload and is associated with a variety of disease states. However, little is known as to how the disruption of lipid regulation or lipid overload affects cell survival. In this study we investigated how excess diacylglycerol (DG), a cardinal metabolite suspected to mediate lipotoxicity, compromises the survival of yeast cells. We reveal that increased DG achieved by either genetic manipulation or pharmacological administration of 1,2-dioctanoyls-n-glycerol (DOG) triggers necrotic cell death. The toxic effects of DG are linked to glucose metabolism and require a functional Rim101 signaling cascade involving the Rim21-dependent sensing complex and the activation of a calpain-like protease. The Rim101 cascade is an established pathway that triggers a transcriptional response to alkaline or lipid stress. We propose that the Rim101 pathway senses DG-induced lipid perturbation and conducts a signaling response that either facilitates cellular adaptation or triggers lipotoxic cell death. Using established models of lipotoxicity, i.e., high-fat diet in Drosophila and palmitic acid administration in cultured human endothelial cells, we present evidence that the core mechanism underlying this calpain-dependent lipotoxic cell death pathway is phylogenetically conserved.

Place, publisher, year, edition, pages
2018. Vol. 25, no 4, p. 765-781
Keywords [en]
Cell biology, Fatty acids, Lipidomics, Membrane lipids, Molecular biology
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:su:diva-155978DOI: 10.1038/s41418-017-0014-2ISI: 000427923400012PubMedID: 29230001OAI: oai:DiVA.org:su-155978DiVA, id: diva2:1205968
Available from: 2018-05-15 Created: 2018-05-15 Last updated: 2018-05-15Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Diessl, JuttaGraier, Wolfgang F.Büttner, Sabrina
By organisation
Department of Molecular Biosciences, The Wenner-Gren Institute
In the same journal
Cell Death and Differentiation
Biological Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf