Fullerenols hijack lysosomes to disrupt inter-organellar crosstalk and block autophagy pre-activated by mTOR inhibitors for cancer cell PANoptosis

自噬 串扰 PI3K/AKT/mTOR通路 细胞生物学 癌症研究 癌细胞 化学 生物 癌症 信号转导 工程类 细胞凋亡 生物化学 遗传学 电子工程
作者
Hedong Qi,Xue Li,Jing Ma,Jiacheng Sun,Yating Liu,Xin Wang,Kelong Fan,Chunying Shu,Chunru Wang
出处
期刊:Science Bulletin [Elsevier BV]
标识
DOI:10.1016/j.scib.2025.02.034
摘要

Subcellular inter-organellar crosstalk among lysosome, endoplasmic reticulum (ER), and mitochondrion is crucial for cancer cell survival and is a promising target in cancer treatment; however, efficiently disrupting these interactive networks is challenging. Herein, a communication interception strategy is presented, which specifically disrupts inter-organellar crosstalk by lysosomal contents leakage along with their trajectory and pre-activates autophagic flux to augment the lysosome-associated autophagy blocking for preventing the self-repair of this subcellular disorder. Briefly, fullerenols containing multiple hydroxyl groups (MF) tear the lysosomal phospholipid membrane through direct interaction, which causes lysosomal contents (calcium ions and cathepsins) to leak into the cytoplasm, subsequently leading to endoplasmic reticulum stress and mitochondrial dysfunction with redox imbalance and metabolic reprogramming. mTOR inhibitors activate and amplify autophagy, then impaired lysosomes prevent their fusion with autophagosome, and thus autophagy is paralyzed along with autolysosome accumulation. Consequently, the cellular homeostasis is compromised by destroyed inter-organellar networks without self-repair by autophagy, thereby triggering PANoptotic processes and leading to a remarkable anti-tumor therapeutic efficacy in vitro and in vivo. This strategy demonstrates the selective cytotoxicity of non-toxic nanomaterials that interfere with subcellular inter-organellar crosstalk, offering a novel method for designing tumor therapies.
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
刚刚
Orange应助Zj采纳,获得10
刚刚
喵喵发布了新的文献求助10
刚刚
小元同学发布了新的文献求助10
1秒前
2秒前
bjyx发布了新的文献求助10
3秒前
3秒前
健康的雪完成签到,获得积分10
3秒前
5秒前
fzy发布了新的文献求助10
6秒前
renzhiqiang发布了新的文献求助10
6秒前
希望天下0贩的0应助泡泡采纳,获得10
7秒前
lan完成签到 ,获得积分10
7秒前
乐观小之应助明亮冰颜采纳,获得10
8秒前
年轻的仙人掌完成签到,获得积分10
8秒前
皮雁子发布了新的文献求助10
8秒前
曲聋五完成签到 ,获得积分0
8秒前
9秒前
寻觅发布了新的文献求助10
9秒前
9秒前
11秒前
Sunjz完成签到,获得积分10
12秒前
弓纪世发布了新的文献求助10
13秒前
roachy发布了新的文献求助10
14秒前
cc关闭了cc文献求助
14秒前
diaoyulao完成签到,获得积分10
14秒前
fzy完成签到,获得积分10
14秒前
皮雁子完成签到,获得积分10
14秒前
14秒前
慕青应助科研通管家采纳,获得10
15秒前
15秒前
科目三应助科研通管家采纳,获得10
15秒前
李爱国应助科研通管家采纳,获得10
15秒前
ED应助科研通管家采纳,获得10
15秒前
李健应助科研通管家采纳,获得10
15秒前
15秒前
15秒前
斯文败类应助科研通管家采纳,获得10
15秒前
DD应助科研通管家采纳,获得10
15秒前
DD应助科研通管家采纳,获得10
15秒前
高分求助中
The Mother of All Tableaux Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 2400
Ophthalmic Equipment Market by Devices(surgical: vitreorentinal,IOLs,OVDs,contact lens,RGP lens,backflush,diagnostic&monitoring:OCT,actorefractor,keratometer,tonometer,ophthalmoscpe,OVD), End User,Buying Criteria-Global Forecast to2029 2000
Cognitive Neuroscience: The Biology of the Mind 1000
Cognitive Neuroscience: The Biology of the Mind (Sixth Edition) 1000
Optimal Transport: A Comprehensive Introduction to Modeling, Analysis, Simulation, Applications 800
Official Methods of Analysis of AOAC INTERNATIONAL 600
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 588
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 3958292
求助须知:如何正确求助?哪些是违规求助? 3504494
关于积分的说明 11118663
捐赠科研通 3235777
什么是DOI,文献DOI怎么找? 1788457
邀请新用户注册赠送积分活动 871211
科研通“疑难数据库(出版商)”最低求助积分说明 802582