Pavel Barahtjan

@pavelbarahtjan.bsky.social

Lipids | Membranes | Tardigrades | Chemical Biology | PostDoc @EPFL | Alumnus @MPICBB

Very happy to share our work on Ether lipid remodeling and ferroptosis. This was a very fruitful collaboration with @harayamajrlab.bsky.social . Many thanks to @giodang.bsky.social for the support and guidance, and to Howard Riezman, where part of this story began. www.biorxiv.org/content/10.6...

Ether lipid remodeling during neuronal differentiation prevents ferroptosis

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

biorxiv.org

BIG ANNOUNCEMENT📣: I haven’t been this excited to be part of something new in 15 years… Thrilled to reveal the passion project I’ve been working on for the past year and a half!🙀🥳 (thread 👇)

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🌶️ Lipids bring the heat 🔥 Lipids don’t just shape membranes, they influence cellular metabolism. We show that tuning lipidome composition strongly alters metabolic heat flow in the minimal cell JCVI-Syn3B 🦠 Fantastic collaboration with Karim Fahmy’s lab (HZDR) 🎉 www.biorxiv.org/content/10.1...

Metabolic heat flow from the minimal cell JCVI-Syn3B reveals the lipidome-dependence of growth and metabolism

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...

biorxiv.org

Think biosensors that give absolute measurement values! So happy this is out :) congrats to everyone involved, especially @sascha-kuhn.bsky.social and @nadlerlab.bsky.social

André Nadler@nadlerlab.bsky.social · last yr.

Meet GEQO: Genetically-encoded biosensors for absolute small-molecule quantification in single cells brought to you by @sascha-kuhn.bsky.social. For simple absolute quantification of your favourite small molecule or ion, head on over to @bioarxiv and read our new preprint: doi.org/10.1101/2025...