Institute of Physics
Nicolaus Copernicus University in Torun, Poland
How to avoid cell death by lipid peroxidation? Unraveling molecular mechanisms and inhibition of ferroptosis.
Recent years have brought attention to ferroptosis, an iron- and lipid peroxidation-dependent form of regulated cell death implicated in a broad range of diseases, including Alzheimer’s and Parkinson’s disease, acute brain injury, sepsis, or asthma. Ferroptosis characteristic feature is the enhanced lipid peroxidation where abstraction of H-atoms from polyunsaturated phospholipids drives the entire peroxidation process causing membrane damage. We demonstrated that a protein complex composed of 15-lipoxygenase and PE-binding protein 1 is a master promoter of ferroptotic cell-death signaling regulated by several enzymatic mechanisms (Cell 2017).
Our primary objective is to target the enzymatic mechanisms underlying ferroptosis at the molecular level. By employing computational approaches such as molecular dynamics simulations, molecular docking, elastic network models, and bioinformatics, in conjunction with the experimental verification, we elucidated previously unknown mechanisms and factors affecting or blocking ferroptosis, thus providing molecular insights of the catalytic processes involved (JACS, J Clin Invest 2018, JCIM 2019).
Furthermore , our recent studies uncover the critical role of iNOS/nitric oxide (Nature Chem Biol 2020, IJMS 2021) and phospholipase iPLA2β (Nature Chem Biol 2021) in regulating ferroptosis. Additionally, we have resolved a paradox concerning Ferrostatin-1, the most commonly used ferroptosis inhibitor (Redox Biol 2021) and we proposed new inhibitors of the human complex that can effectively block the ferroptotic cell death signal (PNAS 2023). Through our research, we have demonstrated the efficacy of computational studies in elucidating and inhibiting fundamental biological processes.
Host: Ivet Bahar
Refreshments following the seminar in room 110