The Research on Ferritinophagy, Ferroptosis and Related Diseases
10.13865/j.cnki.cjbmb.2022.01.1497
- Author:
Hai-Chao MI
1
;
Min SHI
1
;
Fang CUI
2
Author Information
1. Department of Clinical Laboratory, Second Hospital of Hebei Medical University
2. Department of Electron Microscopy Laboratory Centre, Hebei Medical University
- Publication Type:Journal Article
- Keywords:
ferritinophagy;
ferroptosis;
iron metabolism;
nuclear receptor co-activator 4 (NCOA4)
- From:
Chinese Journal of Biochemistry and Molecular Biology
2022;38(9):1133-1140
- CountryChina
- Language:Chinese
-
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.
