Receptor-mediated mitophagy regulates EPO production and protects against renal anemia

Autor: Quan Chen, Ding Wang, Yushan Zhu, Linbo Chen, Tian Zhao, Chenglong Mu, Jinhua Liu, Jie Gao, Changlu Xu, Jiaxi Zhou, Lihong Shi, Yue Li, Yandong Yan Pei, Guangfeng Geng, Jing Liang, Chuanmei Zhang
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Mouse
renal EPO-producing cells
Mitochondrion
Mice
0302 clinical medicine
hemic and lymphatic diseases
Mitophagy
Erythropoiesis
Biology (General)
Kidney
General Neuroscience
Anemia
General Medicine
Haematopoiesis
medicine.anatomical_structure
030220 oncology & carcinogenesis
Medicine
Kidney Diseases
medicine.symptom
medicine.drug
Research Article
QH301-705.5
Science
stress erythropoiesis
Inflammation
General Biochemistry
Genetics and Molecular Biology
Proinflammatory cytokine
Mitochondrial Proteins
03 medical and health sciences
medicine
Animals
Erythropoietin
General Immunology and Microbiology
business.industry
Membrane Proteins
Cell Biology
Mice
Inbred C57BL
030104 developmental biology
Fundc1
Gene Expression Regulation
inflammation
Cancer research
business
Reactive Oxygen Species
Zdroj: eLife
eLife, Vol 10 (2021)
ISSN: 2050-084X
Popis: Erythropoietin (EPO) drives erythropoiesis and is secreted mainly by the kidney upon hypoxic or anemic stress. The paucity of EPO production in renal EPO-producing cells (REPs) causes renal anemia, one of the most common complications of chronic nephropathies. Although mitochondrial dysfunction is commonly observed in several renal and hematopoietic disorders, the mechanism by which mitochondrial quality control impacts renal anemia remains elusive. In this study, we showed that FUNDC1, a mitophagy receptor, plays a critical role in EPO-driven erythropoiesis induced by stresses. Mechanistically, EPO production is impaired in REPs in Fundc1-/- mice upon stresses, and the impairment is caused by the accumulation of damaged mitochondria, which consequently leads to the elevation of the reactive oxygen species (ROS) level and triggers inflammatory responses by up-regulating proinflammatory cytokines. These inflammatory factors promote the myofibroblastic transformation of REPs, resulting in the reduction of EPO production. We therefore provide a link between aberrant mitophagy and deficient EPO generation in renal anemia. Our results also suggest that the mitochondrial quality control safeguards REPs under stresses, which may serve as a potential therapeutic strategy for the treatment of renal anemia.
Databáze: OpenAIRE
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