GSTP1-mediated S-glutathionylation of Pik3r1 is a Redox Hub That Inhibits Osteoclastogenesis Through Regulating Autophagic Flux

Overview

Journal Redox Biol

Specialties Biology
Cell Biology
Endocrinology

Date 2023 Mar 4

PMID 36870110

Authors

Xiaoxiao Ji

Jianqiao Hong

Weinan Yang

Minjun Yao

Jie Wang

Guangyao Jiang

Yibo Wang

Congsun Li

Jiyan Lin

Haochen Mou

Chaozhong Li

Sihao Li

Yazhou Chen

Minming Shi

Wei Wang

Fei Lu

Haobo Wu

Xiang Zhao

Yiying Qi

Shigui Yan

Affiliations

Soon will be listed here.

Abstract

Glutathione S-transferase P1(GSTP1) is known for its transferase and detoxification activity. Based on disease-phenotype genetic associations, we found that GSTP1 might be associated with bone mineral density through Mendelian randomization analysis. Therefore, this study was performed both in vitro cellular and in vivo mouse model to determine how GSTP1 affects bone homeostasis. In our research, GSTP1 was revealed to upregulate the S-glutathionylation level of Pik3r1 through Cys498 and Cys670, thereby decreasing its phosphorylation, further controlling the alteration of autophagic flux via the Pik3r1-AKT-mTOR axis, and lastly altering osteoclast formation in vitro. In addition, knockdown and overexpression of GSTP1 in vivo also altered bone loss outcomes in the OVX mice model. In general, this study identified a new mechanism by which GSTP1 regulates osteoclastogenesis, and it is evident that the cell fate of osteoclasts is controlled by GSTP1-mediated S-glutathionylation via a redox-autophagy cascade.

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