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
• Publication Date: 2022-10-06T10:03:04Z
• Authors: Ruru Wang; Yajing Shang; Bin Chen; Feng Xu; Jie Zhang; Zhaoyang Zhang; Xipeng Zhao; Xiangbo Wan; An Xu; Lijun Wu; Guoping Zhao
• Keywords: 0303 health sciences; QH573-671; TOR Serine-Threonine Kinases; Protein Disulfide-Isomerases; Article; 3. Good health; 03 medical and health sciences; Prohibitins; Autophagy; Humans; Disulfides; Cytology; Microtubule-Associated Proteins; Proto-Oncogene Proteins c-akt

Abstract Protein disulfide isomerase (PDI) is an endoplasmic reticulum (ER) enzyme that mediates the formation of bonds, and also a therapeutic target for cancer treatment. Our previous studies found PDI apoptotic signaling by inducing mitochondrial dysfunction. Considering dysfunction major contributor to autophagy, how regulates autophagy remains unclear. Here, we provide evidence high expression in colorectal tumors significantly increases risk metastasis poor prognosis patients. inhibits radio/chemo-induced cell death regulating signaling. Mechanistically, combination GRP78 was enhanced after ER stress, which degradation AKT GRP78, eventually activates mTOR pathway inhibit initiation. In parallel, can directly interact with mitophagy receptor PHB2 mitochondrial, then competitively blocks binding LC3II Collectively, our results identify reduce radio/chemo-sensitivity could be served as potential radio/chemo-therapy.