Large-scale endoplasmic reticulum membrane solidification spatially organises proteins under thermal or metabolic stress
Year: 2026
Type: preprint
Abstract: Organelle homeostasis is a key determinant of cellular fitness, yet how cells remodel their membranes in response to environmental change remains unclear. Here, we identify a temperature- and lipid saturation-dependent transformation of endoplasmic reticulum membranes into giant, rigid, multilamellar tubes in cells and in vivo . These ‘rods’ emerge from demixing of saturated lipids into solid-like domains – a previously unrecognised, large-scale endomembrane phase behaviour, fundamentally distinct from the transient liquid-ordered nanodomains of the plasma membrane. ER-tubulating reticulon-homology proteins are excluded from rods; their segregation drives progressive membrane flattening and ultimately multilayered wrapping. Surfactant-producing alveolar type-II lung cells, enriched in saturated lipids, form rods even at 37°C, demonstrating that native lipid metabolism can induce this transformation. This spatially organizing lipid-protein domain interplay may tune the ER tubule/sheet balance and provide a homeoviscous mechanism to preserve fluidity in the cholesterol-poor ER under thermal or metabolic stress.
Authors: Paul M. Müller, Melissa R. Mikolaj, Elmehdi Belbaraka, Finn Hartstein, Sophia Altinoluk, Björn Perder, Philipp Trnka, Robert-William Welke, Heike Naumann, Nina Taudien, Severine Kunz, Michele Solimena, Ilya Levental, Kandice R. Levental, Andreas Müller, Helge Ewers, Kedar Narayan, Oliver Rocks
Institutions: Max Delbrück Center, Freie Universität Berlin, National Institutes of Health, Frederick National Laboratory for Cancer Research, National Cancer Institute, Center for Cancer Research, Charité - Universitätsmedizin Berlin, Helmholtz Munich, German Center for Diabetes Research, University Hospital Carl Gustav Carus, Paul Langerhans Institute Dresden, Technische Universität Dresden, University of Virginia
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7154118937