Nuclear receptor co-activator 4 (NCOA4) acts as a selective cargo receptor that binds to ferritin, a cytoplasmic iron storage complex. By mediating ferritinophagy, NCOA4 regulates iron metabolism and releases free iron in the body, thus playing a crucial role in a variety of biological processes, including growth, development, and metabolism. Recent studies have shown that NCOA4-mediated ferritinophagy is closely associated with the occurrence and development of iron metabolism-related diseases, such as liver fibrosis, renal cell carcinoma, and neurodegenerative diseases. In addition, a number of clinical drugs have been identified to modulate NCOA4-mediated ferritinophagy, significantly affecting disease progression and treatment efficacy. This paper aims to review the current research progress on the role of NCOA4-mediated ferritinophagy in related diseases, in order to provide new ideas for targeted clinical therapy.
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Sheng Li Xue Bao
February 2025
Department of Clinical Laboratory, the Second Hospital of Hebei Medical University, Shijiazhuang 050000, China.
Nuclear receptor co-activator 4 (NCOA4) acts as a selective cargo receptor that binds to ferritin, a cytoplasmic iron storage complex. By mediating ferritinophagy, NCOA4 regulates iron metabolism and releases free iron in the body, thus playing a crucial role in a variety of biological processes, including growth, development, and metabolism. Recent studies have shown that NCOA4-mediated ferritinophagy is closely associated with the occurrence and development of iron metabolism-related diseases, such as liver fibrosis, renal cell carcinoma, and neurodegenerative diseases.
View Article and Find Full Text PDFAdv Sci (Weinh)
March 2025
Department of Otolaryngology Head and Neck Surgery, Affiliated Drum Tower Hospital, Medical School of Nanjing University, No. 321 Zhongshan Road, Nanjing, 210008, China.
Cisplatin can cause irreversible hearing loss. However, effective approaches to its prevention are not established. In this study, the effect of the traditional Chinese medicine monomer pinoresinol diglucoside (PDG) is evaluated on cisplatin-induced ototoxicity and its underlying mechanism of action.
View Article and Find Full Text PDFACS Chem Biol
February 2025
Department of Chemistry, State University of New York, Potsdam, New York 13676, United States.
Ferritin degradation pathways, particularly NCOA4-mediated ferritinophagy, are crucial for maintaining iron homeostasis. Here, we demonstrate the coexistence of two NCOA4 isoforms, one iron-sulfur cluster-free and one iron-sulfur cluster-bound, in oxygenated cell cultures. Using a combination of spectroscopic and analytical techniques, in vitro characterization of the NCOA4 fragment (383-522), denoted NCOA4-D, revealed a predominance of monomeric species with a relatively stable [2Fe-2S] cluster under normoxic conditions.
View Article and Find Full Text PDFChem Biol Interact
March 2025
Institute for Applied Research in Public Health, Department of Occupational Medicine and Environmental Toxicology, Nantong Key Laboratory of Environmental Toxicology, School of Public Health, Nantong University, Nantong, 226019, China. Electronic address:
Recently, our group identified antimony (Sb) as a novel nerve pollutant, can lead to neuronal injure. However, Sb-associated neurotoxicological mechanisms yet remain unclear. Herein, we found Sb induced hippocampal neuronal ferroptosis in vivo and in vitro.
View Article and Find Full Text PDFInt Immunopharmacol
March 2025
Orthopedic Center, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou 510000 China; The Second School of Clinical Medicine, Southern Medical University, Guangzhou 510000 China; Orthopaedic Center, Guangdong Second Provincial General Hospital, Guangzhou 510000 China; Zhaoqing Central People's Hospital, Zhaoqing, Guangdong 526000, China. Electronic address:
Ferritinophagy is a specific type of autophagy that maintains intracellular iron metabolic homeostasis by targeting ferritin, one of the major forms of iron storage in the human body. Previous research has demonstrated that quercetin prevents the ferroptosis of oligodendrocyte progenitor cells (OPCs) by inhibiting the Id2/transferrin pathway. Given the ability of quercetin to suppress autophagy in spinal cord injury (SCI), this study aimed to investigate whether quercetin prevents ferroptosis in an autophagy-dependent manner.
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