亲爱的研友该休息了!由于当前在线用户较少,发布求助请尽量完整地填写文献信息,科研通机器人24小时在线,伴您度过漫漫科研夜!身体可是革命的本钱,早点休息,好梦!

Acetylation of mtHSP70 at Lys595/653 affecting its interaction between GrpEL1 regulates glioblastoma progression via UPRmt

胶质母细胞瘤 乙酰化 线粒体 细胞生物学 癌症研究 生物 基因 生物化学
作者
Bixi Gao,Zongqi Wang,Kun Dai,Yunjiang Wang,Long‐Yuan Li,Guangzhao Li,Xiaowang Niu,Xiang Li,Zhengquan Yu,Zhong Wang,Gang Chen
出处
期刊:Free Radical Biology and Medicine [Elsevier BV]
卷期号:213: 394-408 被引量:2
标识
DOI:10.1016/j.freeradbiomed.2024.01.035
摘要

The mitochondrial unfolded protein response (UPRmt) is a vital biological process that regulates mitochondrial protein homeostasis and enables glioblastoma cells to cope with mitochondrial oxidative stress in the tumor microenvironment. We previously reported that the binding of mitochondrial stress-70 protein (mtHSP70) to GrpE protein homolog 1 (GrpEL1) is involved in the regulation of the UPRmt. However, the mechanisms regulating their binding remain unclear. Herein, we examined the UPRmt in glioblastoma and explored whether modulating the interaction between mtHSP70 and GrpEL1 affects the UPRmt. Western blot analysis, aggresome staining, and transmission electron microscopy were used to detect the activation of the UPRmt and protein aggregates within mitochondria. Molecular dynamics simulations were performed to investigate the impact of different mutations in mtHSP70 on its binding to GrpEL1. Endogenous site-specific mutations were introduced into mtHSP70 in glioblastoma cells using CRISPR/Cas9. In vitro and in vivo experiments were conducted to assess mitochondrial function and glioblastoma progression. The UPRmt was activated in glioblastoma cells in response to oxidative stress. mtHSP70 regulated mitochondrial protein homeostasis by facilitating UPRmt-progress protein import into the mitochondria. Acetylation of mtHSP70 at Lys595/653 enhanced its binding to GrpEL1. Missense mutations at Lys595/653 increased mitochondrial protein aggregates and inhibited glioblastoma progression in vitro and in vivo. We identified an innovative mechanism in glioblastoma progression by which acetylation of mtHSP70 at Lys595/653 influences its interaction with GrpEL1 to regulate the UPRmt. Mutations at Lys595/653 in mtHSP70 could potentially serve as therapeutic targets and prognostic indicators of glioblastoma.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
chenting完成签到 ,获得积分10
21秒前
小付完成签到,获得积分10
29秒前
NexusExplorer应助科研通管家采纳,获得10
56秒前
烟消云散完成签到,获得积分10
59秒前
汉堡包应助梦梦采纳,获得10
1分钟前
1分钟前
Orange应助reerwt采纳,获得10
1分钟前
annis完成签到,获得积分10
1分钟前
1分钟前
含蓄绿竹完成签到 ,获得积分10
1分钟前
2分钟前
reerwt发布了新的文献求助10
2分钟前
Liufgui应助sss采纳,获得10
2分钟前
梦梦完成签到,获得积分10
2分钟前
2分钟前
reerwt完成签到,获得积分20
2分钟前
2分钟前
陈元元K完成签到,获得积分10
2分钟前
英俊的铭应助科研通管家采纳,获得10
2分钟前
小二郎应助科研通管家采纳,获得10
2分钟前
3分钟前
梦梦发布了新的文献求助10
3分钟前
3分钟前
caca完成签到,获得积分0
3分钟前
科研通AI2S应助YYYCCCCC采纳,获得10
3分钟前
海鸥别叫了完成签到 ,获得积分10
4分钟前
云霞完成签到 ,获得积分10
4分钟前
朴素的山蝶完成签到 ,获得积分10
4分钟前
4分钟前
FashionBoy应助科研通管家采纳,获得10
4分钟前
Bugs完成签到,获得积分10
5分钟前
5分钟前
小八统治世界完成签到 ,获得积分10
5分钟前
tang完成签到,获得积分10
5分钟前
汉堡包应助舒服的觅夏采纳,获得10
5分钟前
suicone完成签到,获得积分10
5分钟前
zqq完成签到,获得积分0
5分钟前
5分钟前
归陌完成签到 ,获得积分10
5分钟前
6分钟前
高分求助中
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3990045
求助须知:如何正确求助?哪些是违规求助? 3532108
关于积分的说明 11256354
捐赠科研通 3270943
什么是DOI,文献DOI怎么找? 1805146
邀请新用户注册赠送积分活动 882270
科研通“疑难数据库(出版商)”最低求助积分说明 809228