Senolysis by GLS1 Inhibition Ameliorates Kidney Aging by Inducing Excessive mPTP Opening through MFN1,The Journals of Gerontology Series A: Biological Sciences and Medical Sciences

当前位置： X-MOL 学术 › J. Gerontol. A Biol. Sci. Med. Sci. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Senolysis by GLS1 Inhibition Ameliorates Kidney Aging by Inducing Excessive mPTP Opening through MFN1
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences ( IF 4.3 ) Pub Date : 2024-12-19 , DOI: 10.1093/gerona/glae294
Yuting Chen, Nan Zhao, Yu Zhang, Xueqi Chen, Yi Chen, Yifan Wang, Jianqing Wu, Weihong Zhao

Cellular senescence is a pivotal contributor to aging and age-related diseases. The targeted elimination of senescent cells, known as senolysis, has emerged as a promising therapeutic strategy for mitigating these conditions. Glutaminase 1 (GLS1), a key enzyme in the glutaminolysis pathway, has been implicated in various cellular senescence processes. However, its specific role in senescent renal tubular epithelial cells (TECs) remains unclear. This study investigates the role and underlying mechanisms of GLS1 in senescent TECs. Using D-galactose (D-gal)-induced senescence of HK-2 cells, we found that GLS1 inhibition eliminated senescent TECs by promoting excessive mitochondrial permeability transition pore (mPTP) opening. Mechanistically, the excessive mPTP opening is associated with upregulation of mitofusin 1 (MFN1). Inhibition of GLS1 in D-gal-treated HK-2 cells induced a shift in mitochondrial dynamics from fission to fusion, accompanied by a significant increase in MFN1 expression. Knocking down MFN1 reduced the mPTP opening and the expression of mPTP-related genes (PPIF, VDAC and BAX) in cells co-treated with D-gal and the GLS1 inhibitor BPTES. Moreover, treatment of aged mice with BPTES specifically eliminated senescent TECs and ameliorated age-associated kidney disease. These findings reveal that GLS1 inhibition eliminate senescent TECs by promoting excessive mPTP opening, suggesting that targeting GLS1 may be a novel senolytic strategy for alleviating aging-related kidney diseases.

更新日期：2024-12-19

点击分享查看原文

点击收藏

阅读更多本刊新发论文