南京大学李朝军、方雷研究团队近日取得一项新成果。他们报道了新生小鼠心脏中与心脏代谢重编程相关的蛋白质乳酰化表征。2024年3月11日出版的《遗传学报》发表了这项成果。

课题组人员发现心脏代谢重编程可以通过改变全局蛋白乳酰化来调节。通过对出生后第1、5、7天的小鼠心脏进行4D无标记蛋白质组学和赖氨酸乳酰化（Kla）组学分析，鉴定出980个蛋白的2297个Kla位点，其中409个蛋白的1262个Kla位点被量化。功能聚类分析表明，Kla位点改变的蛋白主要参与代谢过程。糖酵解蛋白的表达与Kla水平呈正相关，脂肪酸氧化蛋白的表达与Kla水平呈负相关。

此外，课题组验证了几种不同修饰蛋白的Kla水平，包括ACAT1、ACADL、ACADVL、PFKM、PKM和NPM1。总的来说，他们的研究报道了新生小鼠心脏中的全面Kla图谱，这将有助于理解代谢重编程和心脏再生的调控网络。

研究人员表示，在哺乳动物中，新生儿的心脏可以在出生后短时间内再生，而成年动物则失去这种能力。已经证明代谢重编程对于新生儿心脏中心肌细胞增殖至关重要。

附：英文原文

Title: Characterization of protein lactylation in relation to cardiac metabolic reprogramming in neonatal mouse hearts

Author: anonymous

Issue&Volume: 2024/03/11

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. Herein, we reveal that cardiac metabolic reprogramming could be regulated by altering global protein lactylation. Through performing 4D label-free proteomics and lysine lactylation (Kla) omics analyses in postnatal day 1, 5, and 7 mouse hearts, 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 aid in understanding the regulatory network of metabolic reprogramming and cardiac regeneration.

DOI: 10.1016/j.jgg.2024.02.009

Source: https://www.sciencedirect.com/science/article/abs/pii/S1673852724000559