The characterization of protein lactylation in relation to cardiac metabolic reprogramming in neonatal mouse hearts

Tongyu Zhang; Yingxi Zhu; Xiaochen Wang; Danyang Chong; Haiquan Wang; Dandan Bu; Mengfei Zhao; Lei Fang; Chaojun Li

doi:10.1016/j.jgg.2024.02.009

The characterization of protein lactylation in relation to cardiac metabolic reprogramming in neonatal mouse hearts

J Genet Genomics. 2024 Mar 11:S1673-8527(24)00055-9. doi: 10.1016/j.jgg.2024.02.009. Online ahead of print.

Authors

Tongyu Zhang¹, Yingxi Zhu², Xiaochen Wang¹, Danyang Chong³, Haiquan Wang¹, Dandan Bu¹, Mengfei Zhao¹, Lei Fang⁴, Chaojun Li⁵

Affiliations

¹ Ministry of Education Key Laboratory of Model Animals for Disease Study, Model Animal Research Center, Medical School of Nanjing University, National Resource Center for Mutant Mice, Nanjing, Jiangsu 210093, China.
² State Key Laboratory of Reproductive Medicine and Offspring Health, China International Joint Research Center on Environment and Human Health, Center for Global Health, School of Public Health, Gusu School, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
³ Ministry of Education Key Laboratory of Model Animals for Disease Study, Model Animal Research Center, Medical School of Nanjing University, National Resource Center for Mutant Mice, Nanjing, Jiangsu 210093, China; State Key Laboratory of Reproductive Medicine and Offspring Health, China International Joint Research Center on Environment and Human Health, Center for Global Health, School of Public Health, Gusu School, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
⁴ Ministry of Education Key Laboratory of Model Animals for Disease Study, Model Animal Research Center, Medical School of Nanjing University, National Resource Center for Mutant Mice, Nanjing, Jiangsu 210093, China. Electronic address: njfanglei@nju.edu.cn.
⁵ Ministry of Education Key Laboratory of Model Animals for Disease Study, Model Animal Research Center, Medical School of Nanjing University, National Resource Center for Mutant Mice, Nanjing, Jiangsu 210093, China; State Key Laboratory of Reproductive Medicine and Offspring Health, China International Joint Research Center on Environment and Human Health, Center for Global Health, School of Public Health, Gusu School, Nanjing Medical University, Nanjing, Jiangsu 211166, China. Electronic address: lichaojun@njmu.edu.cn.

PMID: 38479452
DOI: 10.1016/j.jgg.2024.02.009

Abstract

In mammals, the neonatal heart can regenerate upon injury within a short time after birth, while adults lose this ability. Metabolic reprogramming has been demonstrated to be critical for cardiomyocyte proliferation in the neonatal heart. Here, we reveal that cardiac metabolic reprogramming could be regulated by altering global protein lactylation. By performing 4D label-free proteomics and lysine lactylation (Kla) omics analyses in mouse hearts at postnatal days 1, 5, and 7, 2297 Kla sites from 980 proteins are identified, among which 1262 Kla sites from 409 proteins are quantified. Functional clustering analysis reveals that the proteins with altered Kla sites are mainly involved in metabolic processes. The expression and Kla levels of proteins in glycolysis show a positive correlation while a negative correlation in fatty acid oxidation. Furthermore, we verify the Kla levels of several differentially modified proteins, including ACAT1, ACADL, ACADVL, PFKM, PKM, and NPM1. Overall, our study reports a comprehensive Kla map in the neonatal mouse heart, which will help to understand the regulatory network of metabolic reprogramming and cardiac regeneration.

Keywords: Cell proliferation; Lactylation; Metabolic reprogramming; Postnatal heart regeneration.