Membrane Heterogeneity Beyond the Plasma Membrane

Abstract

The structure and organization of cellular membranes have received intense interest, particularly in investigations of the raft hypothesis. The vast majority of these investigations have focused on the plasma membrane of mammalian cells, yielding significant progress in understanding membrane heterogeneity in terms of lipid composition, molecular structure, dynamic regulation, and functional relevance. In contrast, investigations on lipid organization in other membrane systems have been comparatively scarce, despite the likely relevance of membrane domains in these contexts. In this review, we summarize recent observations on lipid organization in organellar membranes, including endoplasmic reticulum, Golgi, endo-lysosomes, lipid droplets, and secreted membranes like lung surfactant, milk fat globule membranes, and viral membranes. Across these non-plasma membrane systems, it seems that the biophysical principles underlying lipid self-organization contribute to lateral domains.

Cholesterol promotes both head group visibility and clustering of PI(4,5)P2driving unconventional secretion of Fibroblast Growth Factor 2

“…In particular, reconstituting PI(4,5)P2 in a pure PC lipid background or removing cholesterol from a plasma-membrane-like lipid composition resulted in decreased binding efficiency of FGF2 to PI(4,5)P2 (23,24). In the light of cholesterol being known to exert profound effects on the organization of the plasma membrane with the lateral segregation into liquidordered and liquid-disordered domains being one example (29)(30)(31)(32)(33), we addressed a potential role of cholesterol in PI(4,5)P2-dependent FGF2 recruitment and translocation across the plasma membrane, the core step of its unconventional mechanism of secretion. We demonstrate in both biochemical reconstitution experiments and single molecule analyses in living cells that cholesterol enhances both PI(4,5)P2-dependent FGF2 recruitment at the inner plasma membrane leaflet and translocation into the extracellular space.…”

Alterations of Golgi Structural Proteins and Glycosylation Defects in Cancer

“…It not only organizes different glycosidases, glycosyltransferases and sugar transporters in an ordered structure and so they can sequentially modify cargo molecules, but also provides each enzyme with an optical microenvironment (e.g., pH, ion, lipid composition, etc.) to maximize its activity ( Rivinoja et al, 2012 ; Wang et al, 2020 ). Moreover, as the trafficking and processing center of the exocytic and endocytic secretory pathways, the Golgi constantly receives cargo molecules from the ER and endosomes, and thus it needs to maintain its dynamic stack structure to host the Golgi enzymes, and at the same time, allow a constant cargo flow through the Golgi stack at a steady speed.…”

Mitochondrial Cristae Architecture and Functions: Lessons from Minimal Model Systems

“…Whereas there are numerous evidences highlighting the presence of lipid-driven domains in various organelles, only some clues of the existence of such domains are suggested in mitochondria [ 131 ]. A priori , there is no reason why the mitochondrial membranes—and in particular its cristae part— should not follow the general principle of membrane compartmentalization, especially since the existence of mesoscopic CL accumulation have been observed in bacteria [ 132 , 133 , 134 ].…”