The mechanism of ferroptosis and its related diseases

Abstract

Ferroptosis, a regulated form of cellular death characterized by the iron-mediated accumulation of lipid peroxides, provides a novel avenue for delving into the intersection of cellular metabolism, oxidative stress, and disease pathology. We have witnessed a mounting fascination with ferroptosis, attributed to its pivotal roles across diverse physiological and pathological conditions including developmental processes, metabolic dynamics, oncogenic pathways, neurodegenerative cascades, and traumatic tissue injuries. By unraveling the intricate underpinnings of the molecular machinery, pivotal contributors, intricate signaling conduits, and regulatory networks governing ferroptosis, researchers aim to bridge the gap between the intricacies of this unique mode of cellular death and its multifaceted implications for health and disease. In light of the rapidly advancing landscape of ferroptosis research, we present a comprehensive review aiming at the extensive implications of ferroptosis in the origins and progress of human diseases. This review concludes with a careful analysis of potential treatment approaches carefully designed to either inhibit or promote ferroptosis. Additionally, we have succinctly summarized the potential therapeutic targets and compounds that hold promise in targeting ferroptosis within various diseases. This pivotal facet underscores the burgeoning possibilities for manipulating ferroptosis as a therapeutic strategy. In summary, this review enriched the insights of both investigators and practitioners, while fostering an elevated comprehension of ferroptosis and its latent translational utilities. By revealing the basic processes and investigating treatment possibilities, this review provides a crucial resource for scientists and medical practitioners, aiding in a deep understanding of ferroptosis and its effects in various disease situations.

The crystal structure of human ferroptosis suppressive protein 1 in complex with flavin adenine dinucleotide and nicotinamide adenine nucleotide

“…found that tripartite motif containing 21 (TRIM21) binds to FSP1 and mediates its ubiquitination on K322 and K366 residues through K63 linkage in gastrointestinal tumors, leading to tumor progression. However, despite the critical role of FSP1, limited FSP1 inhibitors have been identified so far, with iFSP1 being the most popular one 24 . The molecular mechanisms underlying its effect, as well as its target sites within FSP1 essential for ferroptosis inhibition, remain to be explored.…”

“…However, despite the critical role of FSP1, limited FSP1 inhibitors have been identified so far, with iFSP1 being the most popular one. 24 The molecular mechanisms underlying its effect, as well as its target sites within FSP1 essential for ferroptosis inhibition, remain to be explored. This is primarily attributed to the unresolved crystal structure of FSP1.…”

“… 11 , 12 , 13 , 14 For instance, neurodegenerative disorders, ischemia/reperfusion injuries, and various types of cancers where cells are particularly vulnerable to lipid peroxidation‐induced damage have been reported to be closely linked to ferroptosis. 12 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 Therefore, exploring the role and regulatory mechanisms of ferroptosis in these diseases is critical for novel therapeutic strategies and offers insights into the interplay between ferroptosis and cellular homeostasis. 24 …”

“… 12 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 Therefore, exploring the role and regulatory mechanisms of ferroptosis in these diseases is critical for novel therapeutic strategies and offers insights into the interplay between ferroptosis and cellular homeostasis. 24 …”

“… 29 Notably, FSP1 localizes in MAMs, indicating that it might be involved in regulating the interface between mitochondria and the endoplasmic reticulum and thereby regulating ferroptosis. 27 , 31 Although FSP1 is a key regulator of ferroptosis and several pharmacological agents targeting FSP1 have been discovered, 24 the crystal structure of FSP1 is still unclear. This has hindered the further exploitation of pharmacological agents that can modulate FSP1 activity specifically and effectively.…”