PGAM5 exacerbates acute renal injury by initiating mitochondria-dependent apoptosis by facilitating mitochondrial cytochrome c release  

作　　者：Jing-yao Li Xi-ang Sun Xin Wang Ning-hao Yang Hong-yan Xie Heng-jiang Guo Li Lu Xin Xie Li Zhou Jun Liu Wei Zhang Li-min Lu 

机构地区：[1]Department of Physiology and Pathophysiology,School of Basic Medical Sciences,Fudan University,Shanghai 200032,China [2]Division of Nephrology,Shanghai Ninth People's Hospital,Shanghai Jjiao Tong University School of Medicine,639 Zhizaoju Road,Shanghai 200011,China [3]Department of Physiology and Pathophysiology,School of Basic Medical Sciences,Dali University,Dali,Yunnan 671013,China [4]National Clinical Research Center for Aging and Medicine,Huashan Hospital,Fudan University,Shanghai 200040,China [5]Shanghai Kidney Development and Pediatric Kidney Disease Research Center,Children's Hospital of Fudan University,Shanghai 201102,China

出　　处：《Acta Pharmacologica Sinica》2024年第1期125-136,共12页中国药理学报（英文版）

基　　金：financially supported by the National Natural Science Foundation of China(82070712,81873603 to LML);the Science and Technology Commission of Shanghai Municipality(14DZ2260200,the Project of Shanghai Key Laboratory of Kidneyand Blood Purification).

摘　　要：Acute kidney injury(AKl)is a worldwide public health problem characterized by the massive loss of tubular cells.However,the precise mechanism for initiating tubular cell death has not been fully elucidated.Here,we reported that phosphoglycerate mutase 5(PGAM5)was upregulated in renal tubular epithelial cells during ischaemia/reperfusion or cisplatin-induced AKI in mice.PGAM5 knockout significantly alleviated the activation of the mitochondria-dependent apoptosis pathway and tubular apoptosis.Apoptosis inhibitors alleviated the activation of the mitochondria-dependent apoptosis pathway.Mechanistically,as a protein phosphatase,PGAM5 could dephosphorylate Bax and facilitate Bax translocation to the mitochondrial membrane.The translocation of Bax to mitochondria increased membrane permeability,decreased mitochondrial membrane potential and facilitated the release of mitochondrial cytochrome c(Cyt c)into the cytoplasm.Knockdown of Bax attenuated PGAM5 overexpression-induced Cyt c release and tubular cell apoptosis.Our results demonstrated that the increase in PGAM5-mediated Bax dephosphorylation and mitochondrial translocation was implicated in the development of AkI by initiating mitochondrial Cyt c release and activating the mitochondria-dependent apoptosis pathway.Targeting this axis might be beneficial foralleviatingAKl.

关 键 词：acute kidney injury ischaemia/reperfusion injury APOPTOSIS PGAM5 BAX Cyt c 

分 类 号：R692[医药卫生—泌尿科学]