The COP9 signalosome mediates the Spt23 regulated fatty acid desaturation and ergosterol biosynthesis

Abhishek Sinha, Ran Israeli, Angela Cirigliano, Shalev Gihaz, Beny Trabelcy, Gerhard H. Braus, Yoram Gerchman, Ayelet Fishman, Rodolfo Negri, Teresa Rinaldi, Elah Pick

Research output: Contribution to journalArticlepeer-review

Abstract

The COP9 signalosome (CSN) is a conserved eukaryotic complex, essential for vitality in all multicellular organisms and critical for the turnover of key cellular proteins through catalytic and non-catalytic activities. Saccharomyces cerevisiae is a powerful model organism for studying fundamental aspects of the CSN complex, since it includes a conserved enzymatic core but lacks non-catalytic activities, probably explaining its non-essentiality for life. A previous transcriptomic analysis of an S. cerevisiae strain deleted in the CSN5/RRI1 gene, encoding to the CSN catalytic subunit, revealed a downregulation of genes involved in lipid metabolism. We now show that the S. cerevisiae CSN holocomplex is essential for cellular lipid homeostasis. Defects in CSN assembly or activity lead to decreased quantities of ergosterol and unsaturated fatty acids (UFA); vacuole defects; diminished lipid droplets (LDs) size; and to accumulation of endoplasmic reticulum (ER) stress. The molecular mechanism behind these findings depends on CSN involvement in upregulating mRNA expression of SPT23. Spt23 is a novel activator of lipid desaturation and ergosterol biosynthesis. Our data reveal for the first time a functional link between the CSN holocomplex and Spt23. Moreover, CSN-dependent upregulation of SPT23 transcription is necessary for the fine-tuning of lipid homeostasis and for cellular health.

Original languageEnglish
Pages (from-to)4870-4889
Number of pages20
JournalFASEB Journal
Volume34
Issue number4
DOIs
StatePublished - 1 Apr 2020

Bibliographical note

Publisher Copyright:
© 2020 University of Haifa. The FASEB Journal published by Wiley Periodicals, Inc. on behalf of Federation of American Societies for Experimental Biology.

Keywords

  • COP9 signalosome
  • Csn5
  • Ergosterol
  • NEDD8
  • Ole1
  • Rub1
  • S. cerevisiae
  • Spt23

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Biochemistry
  • Biotechnology

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