Your browser doesn't support javascript.
loading
FUNDC1 interacts with GPx4 to govern hepatic ferroptosis and fibrotic injury through a mitophagy-dependent manner.
Bi, Yaguang; Liu, Shuolin; Qin, Xing; Abudureyimu, Miyesaier; Wang, Lu; Zou, Rongjun; Ajoolabady, Amir; Zhang, Wenjing; Peng, Hu; Ren, Jun; Zhang, Yingmei.
Afiliación
  • Bi Y; Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, China; National Clinical Research Center for Interventional Medicine, Shanghai 200032, China.
  • Liu S; Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, China; National Clinical Research Center for Interventional Medicine, Shanghai 200032, China.
  • Qin X; Department of Cardiology, Xijing Hospital, Air Force Medical University, Xi'an 710032, China.
  • Abudureyimu M; Cardiovascular Department, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China.
  • Wang L; Institute of Digestive Diseases, Xijing Hospital, Air Force Medical University, Xi'an 710032, China; State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Air Force Medical University, Xi'an 710032, China.
  • Zou R; Department of Cardiovascular Surgery, Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510120, Guangdong, China; The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong
  • Ajoolabady A; Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, China.
  • Zhang W; Department of Emergency, Shanghai Tenth People's Hospital, School of Medicine Tongji University, Shanghai 200072, China.
  • Peng H; Department of Emergency, Shanghai Tenth People's Hospital, School of Medicine Tongji University, Shanghai 200072, China.
  • Ren J; Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, China; National Clinical Research Center for Interventional Medicine, Shanghai 200032, China; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, W
  • Zhang Y; Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, China; National Clinical Research Center for Interventional Medicine, Shanghai 200032, China. Electronic address: zhang.yingmei@zs-hospital.sh.cn.
J Adv Res ; 55: 45-60, 2024 Jan.
Article en En | MEDLINE | ID: mdl-36828120
INTRODUCTION: Liver fibrosis is a life-threatening pathological anomaly which usually evolves into advanced liver cirrhosis and hepatocellular carcinoma although limited therapeutic option is readily available. FUN14 domain containing 1 (FUNDC1) is a mitophagy receptor with little information in liver fibrosis. OBJECTIVE: This study was designed to examine the role for FUNDC1 in carbon tetrachloride (CCl4)-induced liver injury. METHODS: GEO database analysis and subsequent validation of biological processes including western blot, immunofluorescence, and co-immunoprecipitation were applied to clarify the regulatory role of FUNDC1 on mitophagy and ferroptosis. RESULTS: Our data revealed elevated FUNDC1 levels in liver tissues of patients with liver fibrotic injury and CCl4-challenged mice. FUNDC1 deletion protected against CCl4-induced hepatic anomalies in mice. Moreover, FUNDC1 deletion ameliorated CCl4-induced ferroptosis in vivo and in vitro. Mechanically, FUNDC1 interacted with glutathione peroxidase (GPx4), a selenoenzyme to neutralize lipid hydroperoxides and ferroptosis, via its 96-133 amino acid domain to facilitate GPx4 recruitment into mitochondria from cytoplasm. GPx4 entered mitochondria through mitochondrial protein import system-the translocase of outer membrane/translocase of inner membrane (TOM/TIM) complex, prior to degradation of GPx4 mainly through mitophagy along with ROS-induced damaged mitochondria, resulting in hepatocyte ferroptosis. CONCLUSION: Taken together, our data favored that FUNDC1 promoted hepatocyte injury through GPx4 binding to facilitate its mitochondrial translocation through TOM/TIM complex, where GPx4 was degraded by mitophagy to trigger ferroptosis. Targeting FUNDC1 may be a promising therapeutic approach for liver fibrosis.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ferroptosis / Neoplasias Hepáticas Límite: Animals / Humans Idioma: En Revista: J Adv Res Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Egipto
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ferroptosis / Neoplasias Hepáticas Límite: Animals / Humans Idioma: En Revista: J Adv Res Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Egipto