Fascinating scientific discoveries are sometimes made by re-examining conventional wisdom. The endoplasmic reticulum (ER) is the largest single membrane structure in eukaryotes. Notably, the cell’s nucleus, in which an organism’s DNA is protected, decoded, and duplicated, is contiguous with the ER. The nucleus comprises two membrane bilayers, the inner and outer nuclear membrane. From a cytoplasmic view, the inner nuclear membrane is the most remote area of the ER. Whereas the ER and the outer membrane are highly active in lipid metabolism (membrane synthesis and fat storage), the inner nuclear membrane was thought to be a metabolically “dark backyard” of the cell - a membrane territory that passively receives all of its lipids from the ER.
However, Max Perutz Labs PhD Student Anete Romanauska and group leader Alwin Köhler decided to take a closer look. By developing genetically-encoded, fluorescent lipid biosensors, the scientists uncovered the existence and metabolic turnover of specific lipids at the inner nuclear membrane. Intriguingly, they showed that the inner nuclear membrane can store lipids by synthesizing nuclear fat-storing organelles called nuclear lipid droplets. These structures connect and communicate with the inner nuclear membrane via membrane bridges. They also identified a protein involved in forming proper membrane bridges between droplets and the inner nuclear membrane. A mutated form of this protein causes congenital lipodystrophy, a rare but severe metabolic disease in humans.
In this study, the two scientists challenge previous ideas about the function of nuclear membranes and open up new avenues for exploring how inner nuclear membrane lipids affect cellular metabolism, as well as the genome and its regulation. Finally, a potential role for the inner nuclear membrane in human metabolic diseases will provide fertile ground for future research.
Anete Romanauska, Alwin Köhler: The inner nuclear membrane is a metabolically active territory that generates nuclear lipid droplets.
Cell, 21 June 2018.