0000000000521086

AUTHOR

Martin Hermansson

Phosphoproteomic analysis accross the yeast life cycle reveals homeostatic regulation of fatty acyl chain-length by phosphorylation of the fatty acid synthase complex

The ability to remodel lipid metabolism under changing conditions is pivotal for cellular functionality and homeostasis. Here, we characterize the regulatory landscape of phosphorylation-based signaling events across the life cycle of Saccharomyces cerevisiae and determine its impact on the regulation of lipid metabolism. Our data show that 50 lipid metabolic proteins are differentially phosphorylated as cells transit between different physiological states. To identify functional phosphosites, we devised a strategy where multiple phosphosites are simultaneously mutated into phosphomimetic or phosphodeficient alleles and mutants are phenotyped by in-depth lipidomics flux analysis. This uncov…

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Regulation of Calcium Channel Activity by Lipid Domain Formation in Planar Lipid Bilayers

The sarcoplasmic reticulum channel (ryanodine receptor) from cardiac myocytes was reconstituted into planar lipid bilayers consisting of 1-palmitoyl-2-oleoyl-phosphatidylethanolamine (POPE) and 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) in varying ratios. The channel activity parameters, i.e., open probability and average open time and its resolved short and long components, were determined as a function of POPE mole fraction (X(PE)) at 22.4 degrees C. Interestingly, all of these parameters exhibited a narrow and pronounced peak at X(PE) approximately 0.80. Differential scanning calorimetric measurements on POPE/POPC liposomes with increasing X(PE) indicated that the lipid bilayer ente…

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The superlattice model of lateral organization of membranes and its implications on membrane lipid homeostasis.

AbstractMost biological membranes are extremely complex structures consisting of hundreds of different lipid and protein molecules. According to the famous fluid-mosaic model lipids and many proteins are free to diffuse very rapidly in the plane of the membrane. While such fast diffusion implies that different membrane lipids would be laterally randomly distributed, accumulating evidence indicates that in model and natural membranes the lipid components tend to adopt regular (superlattice-like) distributions. The superlattice model, put forward based on such evidence, is intriguing because it predicts that 1) there is a limited number of allowed compositions representing local minima in mem…

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