Global profiling of lysine lactylation in human lungs

Abstract

Lactate is closely related to various cellular processes, such as angiogenesis, responses to hypoxia, and macrophage polarization, while regulating natural immune signaling pathways and promoting neurogenesis and cognitive function. Lysine lactylation (Kla) is a novel posttranslational modification, the examination of which may lead to new understanding of the nonmetabolic functions of lactate and the various physiological and pathological processes in which lactate is involved, such as infection, tumorigenesis and tumor development. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), researchers have identified lactylation in human gastric cancer cells and some other species, but no research on lactylation in human lungs has been reported.In this study, we performed global profiling of lactylation in human lungs under normal physiological conditions, and 724 Kla sites in 451 proteins were identified. After comparing the identified proteins with those reported in human lactylation datasets, 141 proteins that undergo lactylation were identified for the first time in this study.Our work expands the database on human lactylation and helps advance the study on lactylation function and regulation under physiological and pathological conditions.

Global Profiling of Lysine Acetylation and Lactylation in Kupffer Cells

“…In contrast, lactylation motif analysis in HEK293T cells favored the amino acid residues K (−6, −1, +4, and +7), alanine (A) (+1, +2, +3, and +6), and G, 54 and motif analysis in healthy human lungs frequently identified isoleucine (I), glutamine (Q), and P residues. 55 However, these results did not reveal defined motifs or patterns. This indicates that profiles of the Kla sites are currently being collected.…”

“…The lactylation motif analysis revealed that K, G, and P were favored (Figure B). In contrast, lactylation motif analysis in HEK293T cells favored the amino acid residues K (−6, −1, +4, and +7), alanine (A) (+1, +2, +3, and +6), and G, and motif analysis in healthy human lungs frequently identified isoleucine (I), glutamine (Q), and P residues . However, these results did not reveal defined motifs or patterns.…”

Global profiling of protein lactylation in Caenorhabditis elegans

“…To define the possible Kla motifs in lactylated proteins, the characteristic sequences of modified sites and their enrichment statistics were obtained by MoMo [28], and the following conservative patterns around lactylated peptides were obtained: xxxxxxAxxx_K_xxxxxxxxxx, xxxxxxVxxx_K_xxxxxxxxxx, and xxxxxxxxxA_K_xxxxxxxxxx (where x indicates a random amino acid residue) (Figure 1E). These motifs differ from those identified in human gastric cancer cells [20] and human lungs [21]. Heatmaps were created for the amino acid sequences surrounding lactylation sites; red indicates high frequency, and green indicates low frequency (Figure 1F).…”

“…gastric cancer cells [20], human lungs [21], etc. However, the function of lactylation in one whole organism has not been thoroughly studied.…”

“…Bioinformatics analysis showed that lactylated proteins were mainly involved in the tricarboxylic acid cycle (TCA cycle) and other metabolic pathways. To this end, we compared with the reported human [18][19][20][21] and rat [24] lactylation datasets.…”