Choline dehydrogenase interacts with SQSTM1 to activate mitophagy and promote coelomocyte survival in Apostichopus japonicus following Vibrio splendidus infection

作     者：Lian-Lian Sun Ying-Fen Dai Mei-Xiang You Cheng-Hua Li Lian-Lian Sun;Ying-Fen Dai;Mei-Xiang You;Cheng-Hua Li

作者机构：State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-productsNingbo UniversityNingboZhejiang 315211China Laboratory for Marine Fisheries Science and Food Production ProcessesQingdao National Laboratory for Marine Science and TechnologyQingdaoShandong 266071China 

出 版 物：《动物学研究(英文)》 (Zoological Research)

年 卷 期：2023年第44卷第5期

页      面：905-918页

核心收录：

学科分类：0710[理学-生物学] 0906[农学-兽医学] 09[农学] 

基　　金：supported by the National Natural Science Foundation of China (32102825) Natural Science Foundation of Zhejiang Province (LQ22C190003) 

主　　题：Choline dehydrogenase Mitophagy SQSTM1 Microtubule-associated protein 1 light chain 3 Apostichopus japonicus 

摘      要：Previous studies have shown that Vibrio splendidus infection causes mitochondrial damage in Apostichopus japonicus coelomocytes,leading to the production of excessive reactive oxygen species(ROS)and irreversible apoptotic cell *** evidence suggests that mitochondrial autophagy(mitophagy)is the most effective method for eliminating damaged mitochondria and ROS,with choline dehydrogenase(CHDH)identified as a novel mitophagy receptor that can recognize non-ubiquitin damage signals and microtubule-associated protein 1 light chain 3(LC3)in ***,the functional role of CHDH in invertebrates is largely *** this study,we observed a significant increase in the mRNA and protein expression levels of *** CHDH(AjCHDH)in response to *** infection and lipopolysaccharide(LPS)challenge,consistent with changes in mitophagy under the same ***,AjCHDH was localized to the mitochondria rather than the cytosol following *** ***,AjCHDH knockdown using si RNA transfection significantly reduced mitophagy levels,as observed through transmission electron microscopy and confocal *** investigation into the molecular mechanisms underlying CHDH-regulated mitophagy showed that AjCHDH lacked an LC3-interacting region(LIR)for direct binding to LC3 but possessed a FB1 structural domain that binds to *** interaction between AjCHDH and SQSTM1 was further confirmed by immunoprecipitation ***,laser confocal microscopy indicated that SQSTM1 and LC3 were recruited by AjCHDH in coelomocytes and HEK293T *** contrast,AjCHDH interference hindered SQSTM1 and LC3 recruitment to the mitochondria,a critical step in damaged mitochondrial ***,AjCHDH interference led to a significant increase in both mitochondrial and intracellular ROS,followed by increased apoptosis and decreased coelomocyte ***,these findings indicate that AjCHDH-mediated mitophagy plays a