Non-histone lactylation: unveiling its functional significance

Area of Science:

• Biochemistry
• Molecular Biology
• Proteomics

Background:

• Lactylation, a posttranslational modification (PTM), was discovered in 2019 and primarily targets lysine residues.
• Initially identified on histones, lactylation is now recognized across numerous non-histone proteins, indicating a broad regulatory role.
• High-throughput proteomics studies have identified extensive lactylated proteins and sites, underscoring its global impact on disease development.

Purpose of the Study:

• To review the latest advancements in understanding the regulatory roles of non-histone protein lactylation.
• To highlight the crucial scientific importance of lactylation in various physiological and pathological processes.
• To summarize the mechanisms by which lactylation influences protein function and cellular processes.

Main Methods:

• Literature review of recent high-throughput proteomics studies.
• Analysis of research on lactyltransferase and delactylase activities.
• Examination of studies detailing lactylation's effects on protein conformation, interactions, activity, and localization.

Main Results:

• Lactylation is catalyzed by lactyltransferase and reversed by delactylase, with enzymes like AARS1/2 implicated.
• Lactylation influences protein spatial conformation, molecular interactions, enzyme activity, and subcellular localization.
• Lactylation is involved in tumor development, cardiovascular diseases, immune cell activation, and psychiatric disorders.

Conclusions:

• Non-histone protein lactylation plays a significant regulatory role in diverse diseases.
• Understanding lactylation mechanisms is crucial for future research and therapeutic strategies.
• Lactylation represents a critical area of study with broad implications for human health.