Format

Send to

Choose Destination
Nat Commun. 2020 Feb 6;11(1):756. doi: 10.1038/s41467-020-14528-1.

Regulation of lipid saturation without sensing membrane fluidity.

Author information

1
Medical Biochemistry and Molecular Biology, Medical Faculty, Saarland University, Kirrberger Strasse 100, Building 61.4, 66421, Homburg, Germany.
2
PZMS, Center for Molecular Signaling (PZMS), Medical Faculty, Saarland University, 66421, Homburg, Germany.
3
MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
4
Department of Integrative Biology and Pharmacology, McGovern Medical School at the University of Texas Health Science Center, Houston, Texas, USA.
5
Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Max-von-Laue-Strasse 3, 60438, Frankfurt, Germany.
6
Institute of Biochemistry, Goethe University Frankfurt, Max-von-Laue-Strasse 9, 60438, Frankfurt, Germany.
7
Institute of Biophysics, Goethe University Frankfurt, 60438, Frankfurt, Germany.
8
Medical Biochemistry and Molecular Biology, Medical Faculty, Saarland University, Kirrberger Strasse 100, Building 61.4, 66421, Homburg, Germany. robert.ernst@uks.eu.
9
PZMS, Center for Molecular Signaling (PZMS), Medical Faculty, Saarland University, 66421, Homburg, Germany. robert.ernst@uks.eu.

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.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center