Regulation of lipid saturation without sensing membrane fluidity

Stephanie Ballweg, Erdinc Sezgin, Milka Doktorova, Roberto Covino, John Reinhard, Dorith Wunnicke, Inga Hänelt, Ilya Levental, Gerhard Hummer and Robert Ernst ()
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Stephanie Ballweg: Saarland University
Erdinc Sezgin: University of Oxford
Milka Doktorova: McGovern Medical School at the University of Texas Health Science Center
Roberto Covino: Max Planck Institute of Biophysics
John Reinhard: Saarland University
Dorith Wunnicke: Goethe University Frankfurt
Inga Hänelt: Goethe University Frankfurt
Ilya Levental: McGovern Medical School at the University of Texas Health Science Center
Gerhard Hummer: Max Planck Institute of Biophysics
Robert Ernst: Saarland University

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: Abstract Cells maintain membrane fluidity by regulating lipid saturation, but the molecular mechanisms of this homeoviscous adaptation remain poorly understood. We have reconstituted the core machinery for regulating lipid saturation in baker’s yeast to study its molecular mechanism. By combining molecular dynamics simulations with experiments, we uncover a remarkable sensitivity of the transcriptional regulator Mga2 to the abundance, position, and configuration of double bonds in lipid acyl chains, and provide insights into the molecular rules of membrane adaptation. Our data challenge the prevailing hypothesis that membrane fluidity serves as the measured variable for regulating lipid saturation. Rather, we show that Mga2 senses the molecular lipid-packing density in a defined region of the membrane. Our findings suggest that membrane property sensors have evolved remarkable sensitivities to highly specific aspects of membrane structure and dynamics, thus paving the way toward the development of genetically encoded reporters for such properties in the future.

Date: 2020
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DOI: 10.1038/s41467-020-14528-1

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