Lactylation, as a novel posttranslational modification, is essential for studying the functions and regulation of proteins in physiological and pathological processes, as well as for gaining in-depth knowledge on the occurrence and development of many diseases, including tumors. However, few studies have examined the protein lactylation of one whole organism. Thus, we studied the lactylation of global proteins in Caenorhabditis elegans to obtain an in vivo lactylome. Using an MS-based platform, we identified 1836 Class I (localization probabilities > 0.75) lactylated sites in 487 proteins. Bioinformatics analysis showed that lactylated proteins were mainly located in the cytoplasm and involved in the tricarboxylic acid cycle (TCA cycle) and other metabolic pathways. Then, we evaluated the conservation of lactylation in different organisms. In total, 41 C. elegans proteins were lactylated and homologous to lactylated proteins in humans and rats. Moreover, lactylation on H4K80 was conserved in three species. An additional 238 lactylated proteins were identified in C. elegans for the first time. This study establishes the first lactylome database in C. elegans and provides a basis for studying the role of lactylation.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/pmic.202300185 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Genetic code expansion reveals site-specific lactylation in living cells reshapes protein functions.
Nat Commun
January 2025
School of Pharmacy, Nanjing University of Chinese Medicine, Xianlindadao No. 138, Nanjing, Jiangsu, China.
Protein lactylation is an emerging field. To advance the exploration of its biological functions, here we develop a comprehensive workflow that integrates proteomics to identify lactylated sites, genetic code expansion (GCE) for the expression of site-specifically lactylated proteins in living cells, and an integrated functional analysis (IFA) platform to evaluate their biological effects. Using a combined wet-and-dry-lab proteomics strategy, we identify a conserved lactylation at ALDOA-K147, which we hypothesize plays a significant biological role.
View Article and Find Full Text PDFNonenzymatic lysine D-lactylation induced by glyoxalase II substrate SLG dampens inflammatory immune responses.
Cell Res
January 2025
National Key Laboratory of Immunity & Inflammation, Second Military Medical University, Shanghai, China.
Immunometabolism is critical in the regulation of immunity and inflammation; however, the mechanism of preventing aberrant activation-induced immunopathology remains largely unclear. Here, we report that glyoxalase II (GLO2) in the glycolysis branching pathway is specifically downregulated by NF-κB signaling during innate immune activation via tristetraprolin (TTP)-mediated mRNA decay. As a result, its substrate S-D-lactoylglutathione (SLG) accumulates in the cytosol and directly induces D-lactyllysine modification of proteins.
View Article and Find Full Text PDFAPP lysine 612 lactylation ameliorates amyloid pathology and memory decline in Alzheimer's disease.
J Clin Invest
January 2025
Growth, Development, and Mental Health of Children and Adolescence Center, Pediatric Research Institute, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.
Article Synopsis
- Posttranslational modification (PTM) of the amyloid precursor protein (APP), particularly lactylation, is linked to the development of Alzheimer's disease (AD), but its specific role is still unclear.
- Research showed reduced APP lactylation in AD patients and models, identifying lysine 612 as a key lactylation site, which affects APP processing and Aβ generation.
- A lactyl-mimicking mutant enhanced APP trafficking and reduced cognitive decline by modifying APP interactions, suggesting that targeting APP lactylation may offer new therapeutic avenues for Alzheimer's disease.
Differences in protein lactylation between pale, soft and exudative and red, firm and non-exudative pork.
Meat Sci
March 2025
State Key Laboratory of Meat Quality Control and Cultured Meat Development, Ministry of Education China, Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control, College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.
This study aimed to understand the development of pale, soft, and exudative (PSE) pork from a new perspective by comparing the differences of lactate-induced protein lactylation and its potential regulators including E1A binding protein p300 (p300) and cAMP response element binding protein (CBP) between PSE and red, firm, and non-exudative (RFN) pork at 1 h postmortem. Results demonstrated that PSE pork presented lower glycogen contents and higher lactate levels than RFN pork (P < 0.05).
View Article and Find Full Text PDFComprehensive analysis of lysine lactylation and its potential biological significance in clear cell renal cell carcinoma.
Eur J Med Res
December 2024
Department of Urology, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, Haikou, China.
Background: Clear cell renal cell carcinoma (ccRCC) is a common histological subtype of malignant renal neoplasm. Protein lysine lactylation (Kla) plays a crucial role in tumor metabolic reprogramming. However, little is known regarding the distribution and potential biological functions of Kla in ccRCC.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!