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

被引:205
作者
Young, Barry P. [1 ]
Shin, John J. H. [1 ]
Orij, Rick [2 ]
Chao, Jesse T. [1 ]
Li, Shu Chen [1 ]
Guan, Xue Li [3 ,4 ]
Khong, Anthony [5 ]
Jan, Eric [5 ]
Wenk, Markus R. [4 ,6 ,7 ]
Prinz, William A. [8 ]
Smits, Gertien J. [2 ]
Loewen, Christopher J. R. [1 ,9 ]
机构
[1] Univ British Columbia, Dept Cellular & Physiol Sci, Vancouver, BC V6T 1Z3, Canada
[2] Univ Amsterdam, Dept Mol Biol & Microbial Food Safety, NL-1018 WV Amsterdam, Netherlands
[3] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, Singapore 119077, Singapore
[4] Univ Geneva, Dept Biochem, CH-1211 Geneva, Switzerland
[5] Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z3, Canada
[6] Natl Univ Singapore, Dept Biol Sci, Singapore 119077, Singapore
[7] Univ Basel, Swiss Trop & Publ Hlth Inst, Basel, Switzerland
[8] NIDDKD, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA
[9] Univ British Columbia, Brain Res Ctr, Vancouver, BC V6T 1Z3, Canada
基金
新加坡国家研究基金会; 加拿大自然科学与工程研究理事会; 英国医学研究理事会; 加拿大创新基金会;
关键词
SACCHAROMYCES-CEREVISIAE; TRANSCRIPTION FACTOR; H+-ATPASE; YEAST; PROTEIN; LOCALIZATION; HOMEOSTASIS; VACUOLAR;
D O I
10.1126/science.1191026
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:1085 / 1088
页数:4
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