Iron deficiency-induced ferritinophagy impairs skeletal muscle regeneration through RNF20-mediated H2Bub1 modification

被引：4

作者：

Che, Yunshu ^{[1
]}

Li, Jinteng ^{[1
]}

Wang, Peng ^{[1
]}

Yu, Wenhui ^{[1
]}

Lin, Jiajie ^{[1
]}

Su, Zepeng ^{[1
]}

Ye, Feng ^{[3
]}

Zhang, Zhaoqiang ^{[1
]}

Xu, Peitao ^{[1
]}

Xie, Zhongyu ^{[1
]}

Wu, Yanfeng ^{[2
]}

Shen, Huiyong ^{[1
]}

机构：

[1] Sun Yat Sen Univ, Affiliated Hosp 8, Dept Orthoped, Shenzhen 518033, Peoples R China

[2] Sun Yat Sen Univ, Affiliated Hosp 8, Ctr Biotherapy, 3025 Shennan Rd, Shenzhen 518000, Peoples R China

[3] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Orthoped, Guangzhou 510120, Peoples R China

来源：

SCIENCE ADVANCES | 2023年 / 9卷 / 46期

基金：

中国国家自然科学基金;

关键词：

INDUCED AUTOPHAGY; RNF20; DIFFERENTIATION; MONOUBIQUITINATION; UBIQUITYLATION; DEGRADATION;

D O I：

10.1126/sciadv.adf4345

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Iron deficiency (ID) is a widespread condition concomitant with disease and results in systemic dysfunction of target tissues including skeletal muscle. Activated by ID, ferritinophagy is a recently found type of selective autophagy, which plays an important role in various physiological and pathological conditions. In this study, we demonstrated that ID-mediated ferritinophagy impeded myogenic differentiation. Mechanistically, ferritinophagy induced RNF20 degradation through the autophagy-lysosomal pathway and then negatively regulated histone H2B monoubiquitination at lysine-120 in the promoters of the myogenic markers MyoD and MyoG, which inhibited myogenic differentiation and regeneration. Conditional knockout of NCOA4 in satellite cells, overexpression of RNF20 or treatment with 3-methyladenine restored skeletal muscle regenerative potential under ID conditions. In patients with ID, RNF20 and H2Bub1 protein expression is downregulated in skeletal muscle. In conclusion, our study indicated that the ferritinophagy-RNF20-H2Bub1 axis is a pathological molecular mechanism underlying ID-induced skeletal muscle impairment, suggesting potential therapeutic prospects.

引用

页数：15