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Science 329 (5995): 1085-1088

Copyright © 2010 by the American Association for the Advancement of Science

Phosphatidic Acid Is a pH Biosensor That Links Membrane Biogenesis to Metabolism

Barry P. Young,1,* John J. H. Shin,1,* Rick Orij,2 Jesse T. Chao,1 Shu Chen Li,1 Xue Li Guan,3,4 Anthony Khong,5 Eric Jan,5 Markus R. Wenk,4,6,7 William A. Prinz,8 Gertien J. Smits,2 Christopher J. R. Loewen1,9,{dagger}

Abstract: Recognition of lipids by proteins is important for their targeting and activation in many signaling pathways, but the mechanisms that regulate such interactions are largely unknown. Here, we found that binding of proteins to the ubiquitous signaling lipid phosphatidic acid (PA) depended on intracellular pH and the protonation state of its phosphate headgroup. In yeast, a rapid decrease in intracellular pH in response to glucose starvation regulated binding of PA to a transcription factor, Opi1, that coordinately repressed phospholipid metabolic genes. This enabled coupling of membrane biogenesis to nutrient availability.

1 Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.
2 Department of Molecular Biology and Microbial Food Safety, University of Amsterdam, Amsterdam, 1018 WV, Netherlands.
3 Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077.
4 Department of Biochemistry, University of Geneva, Sciences II, 30 Quai Ernest Ansermet, CH-1211 Geneva, Switzerland.
5 Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.
6 Department of Biological Sciences National University of Singapore, Singapore 119077.
7 Swiss Tropical and Public Health Institute, University of Basel, Socinstrasse 57, P.O. Box 4002, Basel, Switzerland.
8 Laboratory of Cell Biochemistry and Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
9 The Brain Research Centre, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: christopher.loewen{at}

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