Ferroptosis, a type of cell death driven by iron-dependent lipid peroxidation (LPO), emerged as an attractive therapeutic target for treating cancer and degenerative diseases. Lipids play a major role in the execution of ferroptosis with accumulation of oxidized species leading to the rapture of plasma membrane and ultimately cell death. With lipids serving as a primary substrate for peroxidation chain reaction, the composition and the adaptive capacity of the lipidome can define cell vulnerability to ferroptosis. However, the role of lipidome remodelling and adaptation under pro-ferroptotic conditions is still poorly understood. Therefore, this project aims to expand current understanding on the role of lipid metabolism in ferroptosis by mapping dynamics of lipidome remodelling and oxidation upon induction and execution of ferroptotic cell death at cellular and subcellular levels, and exploring modulatory potential of lipid metabolism by targeting lipid class and type specific pathways.
Involved LMAI members:
Understanding dynamics of lipid metabolism and oxidation in ferroptotic cell death programme
Ferroptosis as a common underlying pathomechanism in tissue ischemia/reperfusion injury
Dysregulated systemic release of metabolic and bioactive lipids along hepatocyte-VLDL axis
Extension of the Lipidomics technology platform to include targeted high-throughput phenotyping of lipid metabolism and its remodelling