PhD Scientific Days 2025

Molecular Medicine IV.

Investigating Ferroptosis and Autophagy Interactions through Integrated Database Analysis

Name of the presenter

Hajdú Bence

Institute/workplace of the presenter

Department of Molecular Biology

Authors

Bence Hajdú¹, Luca Csabai², Tamás Korcsmáros³, Orsolya Kapuy¹

1: Department of Molecular Biology, Institute of Biochemistry and Molecular Biology, Semmelweis University
2: Department of Genetics, Eötvös Loránd University
3: Department of Metabolism, Digestion and Reproduction, Imperial College London

Text of the abstract

Ferroptosis is an iron-dependent, regulated form of cell death characterized by lipid peroxidation, reactive oxygen species (ROS) accumulation, and loss of redox homeostasis. It is morphologically, biochemically, and genetically distinct from other cell death mechanisms. During ferroptosis, key observable phenomena include the accumulation of labile iron, peroxidation of polyunsaturated fatty acids (PUFAs), and excessive production of ROS that mediate further reactions causing chromatin condensation defects, increased membrane density, and outer cell membrane rupture.
Two pathways of ferroptosis have been identified: an extrinsic pathway characterized by increased iron uptake and decreased cysteine/glutamate uptake, and an intrinsic pathway involving the inhibition of glutathione peroxidase 4 (GPX4), a crucial antagonist of ferroptosis that maintains redox homeostasis. Ferroptosis has been implicated in several diseases, including neurodegeneration and inflammatory bowel disease (IBD).
A growing body of evidence suggests a complex interplay between ferroptosis and autophagy; however, further research is needed to clarify the precise molecular interactions between these pathways. To elucidate these connections, we developed an integrated, ferroptosis-specific interaction database. This was achieved by programmatically compiling data from multiple existing sources using Python, leveraging the pandas library for data transformation and the requests library for API calls to external repositories. The resultant graph database, built on SQLite, features a schema compatible with the AutophagyNetDB, facilitating direct pathway analysis and comparison between ferroptosis and autophagy. The database includes ferroptosis-related protein-protein interactions, as well as cell-specific annotations for these interactions. This integrated platform is well-positioned to identify key regulatory nodes and molecular links between ferroptosis and autophagy. By doing so, it will provide valuable insights into their crosstalk and highlight potential therapeutic targets.
SUPPORTED BY THE EKÖP-2024-195 NEW NATIONAL EXCELLENCE PROGRAM OF THE MINISTRY FOR CULTURE AND INNOVATION FROM THE SOURCE OF THE NATIONAL RESEARCH, DEVELOPMENT AND INNOVATION FUND.
SUPPORTED BY THE RICHTER GEDEON TALENTUM FOUNDATION.