Global profiling of the protein lactylome in porcine liver

Given the significant physiological and metabolic similarities between pig liver and human liver, along with the importance of pigs as excellent clinical models (successful xenotransplantation and survival in humans), this study presents for the first time a comprehensive lactylation map of the pig liver, revealing that protein lactylation (Kla) is a widespread and functionally important modification in this metabolically active organ. Through high-resolution mass spectrometry, we conducted a global analysis of lactylated proteins and sites in healthy pig liver, identifying 4,110 Kla sites on 1,486 proteins. Bioinformatics feature analysis indicated that these proteins are mainly located in the cytoplasm, mitochondria, and nucleus, and are significantly enriched in core metabolic pathways including glycolysis, the tricarboxylic acid cycle, and the pentose phosphate pathway. Motif analysis identified specific sequence patterns around lactoylated lysines. Comparative analysis showed that specific histone lactylation sites (such as H3K23, H2AK96, H2BK5) are conserved in pigs, mice, and humans, while also revealing tissue-specific characteristics compared to pig ovarian cells. These findings emphasize the close connection between liver lactylation and cellular energy metabolism, and provide a valuable comparative framework for studying the role of lactylation in human liver physiology and disease.