ROS-mediated BNIP3-dependent mitophagy promotes coelomocyte survival in Apostichopus japonicus in response to Vibrio splendidus infection  

作　　者：Lian-Lian Sun Yi-Na Shao Mei-Xiang You Cheng-Hua Li 

机构地区：[1]State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products,Ningbo University,Ningbo,Zhejiang 315211,China [2]Laboratory for Marine Fisheries Science and Food Production Processes,Qingdao National Laboratory for Marine Science and Technology,Qingdao,Shandong 266071,China [3]State-Province Joint Laboratory of Marine Biotechnology and Engineering,Ningbo University,Ningbo,Zhejiang 315211,China

出　　处：《Zoological Research》2022年第2期285-300,共16页动物学研究（英文）

基　　金：supported by the National Natural Science Foundation of China(32073003,32102825);Natural Science Foundation of Zhejiang Province(LZ19C190001);Key Project from Science Technology Department of Zhejiang Province(2019R52016);K.C.Wong Magna Fund in Ningbo University。

摘　　要：Organisms produce high levels of reactive oxygen species(ROS)to kill pathogens or act as signaling molecules to induce immune responses;however,excessive ROS can result in cell death.To maintain ROS balance and cell survival,mitophagy selectively eliminates damaged mitochondria via mitophagy receptors in vertebrates.In marine invertebrates,however,mitophagy and its functions remain largely unknown.In the current study,Vibrio splendidus infection damaged mitochondrial morphology in coelomocytes and reduced mitochondrial membrane potential(ΔΨm)and mitophagosome formation.The colocalization of mitochondria and lysosomes further confirmed that lipopolysaccharide(LPS)treatment increased mitophagy flux.To explore the regulatory mechanism of mitophagy,we cloned Bcl2/adenovirus E1 B 19 kDa protein-interacting protein 3(BNIP3),a common mitophagy receptor,from sea cucumber Apostichopus japonicus(Aj BNIP3)and confirmed that Aj BNIP3 was significantly induced and accumulated in mitochondria after V.splendidus infection and LPS exposure.At the mitochondrial membrane,Aj BNIP3 interacts with microtubule-associated protein 1 light chain 3(LC3)on phagophore membranes to mediate mitophagy.After Aj BNIP3 interference,mitophagy flux decreased significantly.Furthermore,Aj BNIP3-mediated mitophagy was activated by ROS following the addition of exogenous hydrogen peroxide(H2 O2),ROS scavengers,and ROS inhibitors.Finally,inhibition of BNIP3-mediated mitophagy by Aj BNIP3 small interfering RNA(si RNA)or high concentrations of lactate increased apoptosis and decreased coelomocyte survival.These findings highlight the essential role of Aj BNIP3 in damaged mitochondrial degradation during mitophagy.This mitophagy activity is required for coelomocyte survival in A.japonicus against V.splendidus infection.

关 键 词：Apostichopus japonicus MITOPHAGY Bcl2/adenovirus E1B 19 kDa protein-interacting protein 3 Reactive oxygen species Microtubule-associated protein 1 light chain 3 

分 类 号：Q41[生物学—生理学]