Protein disulfide isomerase blocks the interaction of LC3II-PHB2 and promotes mTOR signaling to regulate autophagy and radio/chemo-sensitivity

doi:10.1038/s41419-022-05302-w

	Protein disulfide isomerase blocks the interaction of LC3II-PHB2 and promotes mTOR signaling to regulate autophagy and radio/chemo-sensitivity
	Wang, Ruru 1,5; Shang, Yajing 1,4; Chen, Bin 1,5; Xu, Feng 1,5; Zhang, Jie 1,5; Zhang, Zhaoyang 1,5; Zhao, Xipeng 1,3; Wan, Xiangbo 2; Xu, An 1; Wu, Lijun 1,3
刊名	CELL DEATH & DISEASE
	2022-10-06
卷号	13
ISSN号	2041-4889
DOI	10.1038/s41419-022-05302-w
通讯作者	Zhao, Guoping(gpz@ipp.ac.cn)
英文摘要	Protein disulfide isomerase (PDI) is an endoplasmic reticulum (ER) enzyme that mediates the formation of disulfide bonds, and is also a therapeutic target for cancer treatment. Our previous studies found that PDI mediates apoptotic signaling by inducing mitochondrial dysfunction. Considering that mitochondrial dysfunction is a major contributor to autophagy, how PDI regulates autophagy remains unclear. Here, we provide evidence that high expression of PDI in colorectal cancer tumors significantly increases the risk of metastasis and poor prognosis of cancer patients. PDI inhibits radio/chemo-induced cell death by regulating autophagy signaling. Mechanistically, the combination of PDI and GRP78 was enhanced after ER stress, which inhibits the degradation of AKT by GRP78, and eventually activates the mTOR pathway to inhibit autophagy initiation. In parallel, PDI can directly interact with the mitophagy receptor PHB2 in mitochondrial, then competitively blocks the binding of LC3II and PHB2 and inhibits the mitophagy signaling. Collectively, our results identify that PDI can reduce radio/chemo-sensitivity by regulating autophagy, which could be served as a potential target for radio/chemo-therapy.
资助项目	National Natural Science Foundation of China[31870845] ; National Natural Science Foundation of China[12122510] ; National Natural Science Foundation of China[32171240] ; National Natural Science Foundation of China[11835014] ; Anhui Provincial Key RD Programm[202104a07020006] ; HFIPS Director's Fund[BJPY2021B07] ; HFIPS Director's Fund[YZJJZX202014]
WOS关键词	ENDOPLASMIC-RETICULUM STRESS ; ER STRESS ; DNA-REPAIR ; INHIBITION ; RESISTANCE ; GLIOBLASTOMA ; EXPRESSION ; GRP78/BIP ; DISCOVERY ; CHAPERONE
WOS研究方向	Cell Biology
语种	英语
出版者	SPRINGERNATURE
WOS记录号	WOS:000864661900002
资助机构	National Natural Science Foundation of China ; Anhui Provincial Key RD Programm ; HFIPS Director's Fund
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/129321]
专题	中国科学院合肥物质科学研究院
通讯作者	Zhao, Guoping
作者单位	1.Chinese Acad Sci, Key Lab High Magnet Field & Ion Beam Phys Biol, Anhui Prov Key Lab Environm Toxicol & Pollut Cont, High Magnet Field Lab,Hefei Inst Phys Sci, Hefei 230031, Anhui, Peoples R China 2.Sun Yat Sen Univ, Affiliated Hosp 6, Guangzhou 510275, Guangdong, Peoples R China 3.Anhui Univ, Informat Mat & Intelligent Sensing Lab Anhui Prov, Inst Phys Sci & Informat Technol, Hefei 230601, Anhui, Peoples R China 4.Anhui Med Univ, Hefei 230032, Anhui, Peoples R China 5.Univ Sci & Technol China, Hefei 230026, Anhui, Peoples R China
推荐引用方式 GB/T 7714	Wang, Ruru,Shang, Yajing,Chen, Bin,et al. Protein disulfide isomerase blocks the interaction of LC3II-PHB2 and promotes mTOR signaling to regulate autophagy and radio/chemo-sensitivity[J]. CELL DEATH & DISEASE,2022,13.
APA	Wang, Ruru.,Shang, Yajing.,Chen, Bin.,Xu, Feng.,Zhang, Jie.,...&Zhao, Guoping.(2022).Protein disulfide isomerase blocks the interaction of LC3II-PHB2 and promotes mTOR signaling to regulate autophagy and radio/chemo-sensitivity.CELL DEATH & DISEASE,13.
MLA	Wang, Ruru,et al."Protein disulfide isomerase blocks the interaction of LC3II-PHB2 and promotes mTOR signaling to regulate autophagy and radio/chemo-sensitivity".CELL DEATH & DISEASE 13(2022).