Proteomic Profiling of Lysine Acetylation Indicates Mitochondrial Dysfunction in the Hippocampus of Gut Microbiota-Absent Mice

作者全名："Yu, Ying; Wang, Haiyang; Rao, Xuechen; Liu, Lanxiang; Zheng, Peng; Li, Wenxia; Zhou, Wei; Chai, Tingjia; Ji, Ping; Song, Jinlin; Wei, Hong; Xie, Peng"

作者地址："[Yu, Ying; Xie, Peng] Chongqing Med Univ, Coll Lab Med, Key Lab Lab Med Diagnost, Minist Educ, Chongqing, Peoples R China; [Yu, Ying; Wang, Haiyang; Rao, Xuechen; Liu, Lanxiang; Zheng, Peng; Li, Wenxia; Zhou, Wei; Chai, Tingjia; Xie, Peng] Chongqing Med Univ, Key Lab Diag & Treatment Brain Funct Dis, Natl Hlth Commiss, Affiliated Hosp 1, Chongqing, Peoples R China; [Wang, Haiyang; Ji, Ping; Song, Jinlin] Chongqing Med Univ, Coll Stomatol, Chongqing, Peoples R China; [Wang, Haiyang; Ji, Ping; Song, Jinlin] Chongqing Med Univ, Affiliated Stomatol Hosp, Chongqing, Peoples R China; [Rao, Xuechen] Chongqing Med Univ, Coll Biomed Engn, Chongqing, Peoples R China; [Liu, Lanxiang; Xie, Peng] Chongqing Med Univ, Dept Neurol, Yongchuan Hosp, Chongqing, Peoples R China; [Liu, Lanxiang; Zheng, Peng; Xie, Peng] Chongqing Med Univ, Dept Neurol, Affiliated Hosp 1, Chongqing, Peoples R China; [Wei, Hong] Third Mil Med Univ, Dept Lab Anim Sci, Coll Basic Med Sci, Chongqing, Peoples R China"

通信作者："Xie, P (corresponding author), Chongqing Med Univ, Coll Lab Med, Key Lab Lab Med Diagnost, Minist Educ, Chongqing, Peoples R China.; Xie, P (corresponding author), Chongqing Med Univ, Key Lab Diag & Treatment Brain Funct Dis, Natl Hlth Commiss, Affiliated Hosp 1, Chongqing, Peoples R China.; Xie, P (corresponding author), Chongqing Med Univ, Dept Neurol, Yongchuan Hosp, Chongqing, Peoples R China.; Xie, P (corresponding author), Chongqing Med Univ, Dept Neurol, Affiliated Hosp 1, Chongqing, Peoples R China.; Wei, H (corresponding author), Third Mil Med Univ, Dept Lab Anim Sci, Coll Basic Med Sci, Chongqing, Peoples R China."

来源：FRONTIERS IN MOLECULAR NEUROSCIENCE

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:000632413900001

JCR分区：Q2

影响因子：4.8

年份：2021

卷号：14

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：depression; gut microbiota; lysine acetylation; germ-free; mitochondrial

摘要："Major depressive disorder (MDD) is a leading cause of disability around the world and contributes greatly to the global burden of disease. Mounting evidence suggests that gut microbiota dysbiosis may be involved in the pathophysiology of MDD through the microbiota-gut-brain axis. Recent research suggests that epigenetic modifications might relate to depression. However, our knowledge of the role of epigenetics in host-microbe interactions remains limited. In the present study, we used a combination of affinity enrichment and high-resolution liquid chromatography tandem mass spectrometry analysis to identify hippocampal acetylated proteins in germ-free and specific pathogen-free mice. In total, 986 lysine acetylation sites in 543 proteins were identified, of which 747 sites in 427 proteins were quantified. Motif analysis identified several conserved sequences surrounding the acetylation sites, including D*Kac, DKac, KacY, KacD, and D*Kac. Gene ontology annotations revealed that these differentially expressed acetylated proteins were involved in multiple biological functions and were mainly located in mitochondria. In addition, pathway enrichment analysis demonstrated that oxidative phosphorylation and the tricarboxylic acid cycle II (eukaryotic), both of which are exclusively localized to the mitochondria, were the primarily disturbed functions. Taken together, this study indicates that lysine acetylation alterations may play a pivotal role in mitochondrial dysfunction and may be a mechanism by which gut microbiota regulate brain function and behavioral phenotypes."

基金机构："National Key R&D Program of China [2017YFA0505700]; Non-Profit Central Research Institute Fund of the Chinese Academy of Medical Sciences [2019PT320002]; Natural Science Foundation Project of ChinaNational Natural Science Foundation of China (NSFC) [81820108015]; China Postdoctoral Science FoundationChina Postdoctoral Science Foundation [2020TQ0393, 2020M683634XB]"

基金资助正文："This study was supported by the National Key R&D Program of China (Grant No. 2017YFA0505700), the Non-Profit Central Research Institute Fund of the Chinese Academy of Medical Sciences (Grant No. 2019PT320002), the Natural Science Foundation Project of China (Grant No. 81820108015), and the China Postdoctoral Science Foundation (Grant Nos. 2020TQ0393 and 2020M683634XB)."