Phospholipid metabolism regulated by a transcription factor sensing phosphatidic acid on the endoplasmic reticulum.
Christopher Loewen (1), Laura Gaspar (2), Steve Jesch (2), Christine Delon (3), Nicholas Ktistakis (3), Susan Henry (2), Timothy Levine (4)
(1) Division of Cell Biology, Institute of Ophthalmology, UCL, Bath Street, London EC1V 9EL, UK;
(2) Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA;
(3) Signalling Programme, Babraham Institute, Babraham, Cambridge CB2 4AT, UK;
(4) Cell Biology, Institute of Ophthalmology UCL, 11-43 Bath Street, london, EC1V 9EL, UK
All cells control the biophysical properties of their membranes by coordinated regulation of different classes of lipids. We identify a highly dynamic feed-back mechanism by which budding yeast Saccharomyces cerevisiae regulate phospholipid biosynthesis. Phosphatidic acid on the endoplasmic reticulum directly binds the soluble transcriptional repressor Opi1p to maintain it inactive outside the nucleus. Following the addition of the lipid precursor inositol, phosphatidic acid is rapidly consumed, leading to release of Opi1p from the endoplasmic reticulum, nuclear translocation, and repression of target genes. These results demonstrate that phosphatidic acid, an essential ubiquitous intermediate in lipid metabolism, is also a signaling lipid.
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