A Eukaryotic Sensor for Membrane Lipid Saturation

作者：Covino Roberto; Ballweg Stephanie; Stordeur Claudius; Michaelis Jonas B; Puth Kristina; Wernig Florian; Bahrami Amir; Ernst Andreas M; Hummer Gerhard; Ernst Robert^*

来源：Molecular Cell, 2016, 63(1): 49-59.

DOI：10.1016/j.molcel.2016.05.015

Maintaining a fluid bilayer is essential for cell signaling and survival. Lipid saturation is a key factor determining lipid packing and membrane fluidity, and it must be tightly controlled to guarantee organelle function and identity. A dedicated eukaryotic mechanism of lipid saturation sensing, however, remains elusive. Here we show that Mga2, a transcription factor conserved among fungi, acts as a lipid-packing sensor in the ER membrane to control the production of unsaturated fatty acids. Systematic mutagenesis, molecular dynamics simulations, and electron paramagnetic resonance spectroscopy identify a pivotal role of the oligomeric transmembrane helix (TMH) of Mga2 for intra-membrane sensing, and they show that the lipid environment controls the proteolytic activation of Mga2 by stabilizing alternative rotational orientations of the TMH region. This work establishes a eukaryotic strategy of lipid saturation sensing that differs significantly from the analogous bacterial mechanism relying on hydrophobic thickness.

• 出版日期2016-7-7