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Regulation Of Lipid Metabolism By SREBPs
Author(s) -
Espenshade Peter
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.394.2
Subject(s) - sterol regulatory element binding protein , transcription factor , microbiology and biotechnology , lipid metabolism , biology , protease , biochemistry , ubiquitin ligase , chemistry , ubiquitin , gene , enzyme
Lipid synthesis requires molecular oxygen. Consequently, maintenance of cell growth under hypoxic conditions requires adaptive mechanisms that control lipid homeostasis. In mammalian cells, sterol regulatory element‐binding protein (SREBP) transcription factors are central regulators of cellular lipid homeostasis. Our studies in fungi demonstrate that SREBPs are oxygen‐responsive transcription factors required for adaptation to low oxygen and for host infection by pathogenic fungi. In fission yeast, proteolytic release of SREBP in response to low oxygen requires the Golgi membrane‐anchored Dsc E3 ligase complex, but no SREBP protease has yet been identified. Recently, we identified an uncharacterized protease required for SREBP proteolytic processing, and we will present our results on how this protease functions in SREBP activation. In addition, fission yeast SREBP does not activate all lipid synthesis genes under low oxygen, for example, those required for unsaturated fatty acid synthesis. We will present data demonstrating that the transcription factor Mga2 is also oxygen‐responsive and functions as an SREBP‐like transcription factor during hypoxic adaptation. Collectively, these two pathways control lipid homeostasis in response to low oxygen in fission yeast. Support or Funding Information Studies were supported by the National Institutes of Health (HL‐077588).