title: Lysine malonylation is elevated in type 2 diabetic mouse models and enriched in metabolic associated proteins.
abstract: Protein lysine malonylation, a newly identified protein post-translational modification (PTM), has been proved to be evolutionarily conserved and is present in both eukaryotic and prokaryotic cells. However, its potential roles associated with human diseases remain largely unknown. In the present study, we observed an elevated lysine malonylation in a screening of seven lysine acylations in liver tissues of db/db mice, which is a typical model of type 2 diabetes. We also detected an elevated lysine malonylation in ob/ob mice, which is another model of type 2 diabetes. We then performed affinity enrichment coupled with proteomic analysis on liver tissues of both wild-type (wt) and db/db mice and identified a total of 573 malonylated lysine sites from 268 proteins. There were more malonylated lysine sites and proteins in db/db than in wt mice. Five proteins with elevated malonylation were verified by immunoprecipitation coupled with Western blot analysis. Bioinformatic analysis of the proteomic results revealed the enrichment of malonylated proteins in metabolic pathways, especially those involved in glucose and fatty acid metabolism. In addition, the biological role of lysine malonylation was validated in an enzyme of the glycolysis pathway. Together, our findings support a potential role of protein lysine malonylation in type 2 diabetes with possible implications for its therapy in the future.
authors.affiliation: From the ‡National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China;
authors.forename: Yipeng
authors.initials: Y
authors.lastname: Du
authors.affiliation: §Laboratory of Protein and Peptide Pharmaceuticals & Laboratory of Proteomics, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; ‖University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Tanxi
authors.initials: T
authors.lastname: Cai
authors.affiliation: ¶Department of Biomedical Informatics, Peking University Health Science Center, Beijing 100191, China;
authors.forename: Tingting
authors.initials: T
authors.lastname: Li
authors.affiliation: §Laboratory of Protein and Peptide Pharmaceuticals & Laboratory of Proteomics, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China;
authors.forename: Peng
authors.initials: P
authors.lastname: Xue
authors.affiliation: From the ‡National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; ‖University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhou
authors.affiliation: From the ‡National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; ‖University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: He
authors.affiliation: From the ‡National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; ‖University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wei
authors.affiliation: From the ‡National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China;
authors.forename: Pingsheng
authors.initials: P
authors.lastname: Liu
authors.affiliation: §Laboratory of Protein and Peptide Pharmaceuticals & Laboratory of Proteomics, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; weitt@moon.ibp.ac.cn fqyang@ibp.ac.cn.
authors.forename: Fuquan
authors.initials: F
authors.lastname: Yang
authors.affiliation: From the ‡National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; weitt@moon.ibp.ac.cn fqyang@ibp.ac.cn.
authors.forename: Taotao
authors.initials: T
authors.lastname: Wei
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004195:Disease Models, Animal; D008099:Liver / Q000378:metabolism; D008239:Lysine / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000378:metabolism
chemical_list: D011506:Proteins; D008239:Lysine