ABSTRACT
Ferroptosis is an iron-dependent form of regulated cell death,which is distinct from apoptosis,ne-crosis,and pyroptosis.Recent studies have found that activators of ferroptosis,such as Erastin,can activate autophagy-re-lated proteins,induce the formation of autophagosomes,and ultimately release ferric ions to mediate ferroptosis.This pro-cess,called ferritinophagy,is initiated by the binding of an autophagic cargo receptor protein,nuclear receptor coactivator 4(NCOA4),to iron-laden ferritin.The transfer of NCOA4-ferritin to the lysosome by ferritinophagy results in the proteoly-sis of ferritin,and,in turn,the release of its iron content and lipid-reactive oxygen species(ROS)accumulation.Ferritin-ophagy has been closely associated with central nervous system disorders,circulatory system diseases,and cancer.Fur-thermore,the regulation mechanism of ferritinophagy is also a hot topic in the study of iron-dependent cell death process.With the in-depth study of ferritinophagy,great progress has been made in the study of key components of ferritinophagy as well as its molecular mechanisms and processes.However,a comprehensive summary of the methods for detecting ferritin-ophagy is still unclear.To further deepen the understanding of ferritinophagy and its detection methods,this review focus-es on the concept,characteristics,methods,and precautions during detection of ferritinophagy.This review provided ex-perimental reference for subsequent researchers and promoting the progress of research related to ferritinophagy.
ABSTRACT
Abnormal iron metabolism mediated by ferritinophagy is one of the most important mechanisms in the occurrence of ferroptosis.The regulatory mechanism of ferritinophagy mainly involves the transcription of NCOA4 and its corresponding protein modifications.Ferroptosis plays an important role in the development of colitis and colitis-associated cancer,and target-oriented regulation of ferroptosis can alleviate colonic inflammatory response and induce the tumor cell death.This article mainly reviewed the regulatory mechanism of NCOA4-mediated ferritinophagy and its progress in colitis and colitis-related cancer,which may provide a new point for the investigation on mechanism of colitis and inflammation-cancer transformation.
ABSTRACT
Iron, an important cofactor for heme, mitochondrial respiratory chain complexes, and various biologically important enzymes, participates in biological processes including oxygen transport, redox reactions, and metabolite synthesis. Ferritin is an iron storage protein that maintains iron homeostasis in the body by sequestering and releasing iron. Ferritinophagy is a selective type of autophagy that mediates ferritin degradation, releasing free iron when increased intracellular iron level is needed. Moderate rates of iron autophagy maintain intracellular iron content homeostasis. Excessive ferritinophagy will release a large amount of free iron, causing lipid peroxidation and cell damage via reactive oxygen species (ROS) produced by the Fenton reaction. Therefore, ferritinophagy plays a vital role in maintaining cellular iron homeostasis. Nuclear receptor co-activator 4 (NCOA4) acts as a key regulator of ferritinophagy by targeting ferritin binding and delivery to lysosomes for degradation, leading to release of free iron. Thus, NCOA4-mediated ferritinophagy is an important contributor to iron metabolism. Recent research reveals that NCOA4 is regulated by factors including iron content, autophagy, lysosomes, and hypoxia. NCOA4-mediated ferritin degradation is related to ferroptosis (an autophagic cell death process) . Ferritinophagy acts as an upstream mechanism driving ferroptosis by regulating cellular iron homeostasis and ROS production, which are closely correlated with the occurrence and development of anemia, neurodegenerative diseases, cancer, ischemia / reperfusion injury, and other diseases. In this study, the functional characteristics of NCOA4-mediated ferritinophagy in ferroptosis and the role of NCOA4 in these diseases were reviewed, which may provide new avenues for the treatment of related diseases.