Ferroptosis: principles and significance in health and disease

Abstract

Ferroptosis, an iron-dependent form of cell death characterized by uncontrolled lipid peroxidation, is governed by molecular networks involving diverse molecules and organelles. Since its recognition as a non-apoptotic cell death pathway in 2012, ferroptosis has emerged as a crucial mechanism in numerous physiological and pathological contexts, leading to significant therapeutic advancements across a wide range of diseases. This review summarizes the fundamental molecular mechanisms and regulatory pathways underlying ferroptosis, including both GPX4-dependent and -independent antioxidant mechanisms. Additionally, we examine the involvement of ferroptosis in various pathological conditions, including cancer, neurodegenerative diseases, sepsis, ischemia–reperfusion injury, autoimmune disorders, and metabolic disorders. Specifically, we explore the role of ferroptosis in response to chemotherapy, radiotherapy, immunotherapy, nanotherapy, and targeted therapy. Furthermore, we discuss pharmacological strategies for modulating ferroptosis and potential biomarkers for monitoring this process. Lastly, we elucidate the interplay between ferroptosis and other forms of regulated cell death. Such insights hold promise for advancing our understanding of ferroptosis in the context of human health and disease.

Protein modification and degradation in ferroptosis

“…These DAMPs are pivotal in activating the immune response, serving as signals that notify the immune system of the presence of damaged or stressed cells. Both excessive and deficient ferroptosis are implicated in various diseases and pathological conditions, including cancer, tissue ischemia-reperfusion, inflammatory diseases, neurodegeneration, age-related diseases, and tissue damage (e.g., kidney injury) [ [7] , [8] , [9] ]. This discovery has sparked a substantial increase in research on ferroptosis, yielding fresh insights into its molecular and cellular mechanisms, along with its potential applications in disease treatment [ [10] , [11] , [12] ].…”

Editorial: Deregulated signaling pathways in inflammation and cancer

“…Elaborate discussions are included on the roles of Hippo pathway in metabolism, immune response, mucosal barrier, mechanical stress and intestinal tumors. Similarly, the roles of ferroptosis, a regulated cell death resulting from iron accumulation ( Chen et al, 2024 ), in inflammation, immune response, cancer, metabolism and mechanotransduction are also discussed. Interestingly, attention has been drawn to the overlapping roles of Hippo pathway and ferroptosis in intestinal diseases, by specifically calling out potential mediators that bridge these pathways.…”