Lennartz et al. evaluate lipid enrichment in clathrin-coated pits and observe that the differential lipid partitioning into clathrin-coated pits is largely driven by the lipid asymmetry of the plasma ...

Cells undergo membrane remodeling in response to the environment to perform specific functions. Now, a cytometry-based method with immune cell biomarker analysis captures variations in plasma membrane...

Cell fate is shaped by external cues and intrinsic cellular states. While supracellular signals, such as growth factors, provide instructive guidance, emerging evidence highlights the role of cell-aut...

Cell fate is shaped by external cues and intrinsic cellular states. While supracellular signals, such as growth factors, provide instructive guidance, emerging evidence highlights the role of cell-aut...

Cell fate is shaped by external cues and intrinsic cellular states. While supracellular signals, such as growth factors, provide instructive guidance,…

Ferroptosis is a form of cell death driven by iron-dependent lipid peroxidation, with specific lipid species playing key roles in modulating susceptibility. Among these, ether lipids have shown conflicting effects, being linked to both protection and sensitization. Here, we dissect the relationship between lipid structure and ferroptosis sensitivity and explain how ether lipids exert context-dependent effects. Ether lipids can promote ferroptosis through a metabolic bias towards the accumulation of polyunsaturated acyl chains and ethanolamine head groups, whereas this pro-ferroptotic tendency is counterbalanced by the anti-ferroptotic vinyl ether moiety introduced by plasmanylethanolamine desaturase 1. We show that this protective effect is critical for preventing ferroptosis in hiPSC-derived neurons, which accumulate otherwise pro-ferroptotic ether lipids during differentiation. This effect is not solely due to its antioxidant properties but also stems from the reprogramming of mitochondrial respiration. The lack of vinyl ether bonds leads to multiple mitochondrial defects, including increased mitochondrial reactive oxygen species (ROS), lower membrane potential, and abnormal cristae structures. These findings indicate that vinyl ether bonds in ether lipids offer dual ferroptosis resistance by scavenging ROS and minimizing its production at the mitochondrial level. The disruption of this system in Caenorhabditis elegans leads to iron-induced death and impaired motility. Thus, our study reveals ether lipid structural remodeling as a key regulator of ferroptosis sensitivity in neurons. ### Competing Interest Statement The authors have declared no competing interest. Deutsche Forschungsgemeinschaft, AS 647/1-1 Agencia Estatal de Investigación, PID2023-146930NB-I00 Japan Science and Technology Agency, JPMJER2101, JPMJFR230H, JPMJND2305, 25H01425, 25H01426, JPMJAP2505 National Research Agency French government, ANR-25-CE44-1525 Agencia Estatal de Investigación (AEI)-Spain, PID2021-123336NB-C21, PID2024-158644NB-C21 Swiss National Science Foundation, 185898, 184949 CNRS/Inserm ATIP-Avenir, ANR-15-IDEX-01

Bifunctional diazirine lipids are versatile tools for mapping protein–lipid interactions and cellular localization by photo-cross-linking. Yet, the cross-linking efficiency of these probes has not bee...

AbstractSummary. Lipid–protein interactions play essential roles in cellular signaling and membrane dynamics, yet their systematic characterization has lon

DANGELOLAB

Researchers found that the shape of the fluid-filled cavities in the developing pancreas is controlled by pressure and the rate cells divide.

The cell membrane facilitates interactions with the environment and serves as an organizational platform for coordinating cellular processes, with lipids playing a central role in determining membrane...

Nature Methods - uMAIA is an analytical framework designed to enable the construction of metabolic atlases at high resolution using mass spectrometry imaging data.

Directional, non-vesicular lipid transport is responsible for fast, species-selective lipid sorting into organelle membranes.

GR-SCHUHMACHER

Size and shape are critical discriminators between molecular species and states. We describe a microchip-based high-throughput imaging approach offering rapid and precise determination of molecular pr...

Lipids are major cell constituents endowed with astonishing structural diversity. The pathways responsible for the assembly and disposal of different lipid species are energetically demanding, and gen...