Research progress in the role and mechanism of lactylation in diseases

Abstract

Lactic acid is a product of cell respiration. After entering into cells, glucose is metabolized to pyruvate by glycolysis. When the oxygen supply is sufficient, pyruvate is converted to acetyl coenzyme A through pyruvate dehydrogenase in the mitochondrial matrix to participate in the tricarboxylic acid cycle and provide necessary energy for cells. Pyruvate is catalysed by lactate dehydrogenase in the cytoplasm to produce lactate while cells are grown under hypoxic conditions. Lactate not only provides energy for mitochondrial respiration, but also plays important roles in inflammatory responser, wound repair, memory formation and neuroprotection as well as tumor growth and metastasis and other pathophysiological processes through autocrine, paracrine, and endocrine forms, which affects the development and prognosis of diseases. Epigenetic modification regulates gene replication, transcription and translation by covalently adding or hydrolyzing functional groups on histones and DNA through related enzymes and affects the biological effects of cells. Histones are the major structural proteins of eukaryotic chromosomes. Their post-translational modifications, such as methylation and acetylation, affect their affinity with DNA, change chromatin structures, and are widely involved in regulation of gene expression. Recent studies have found that histones can undergo lactylation, which is a new epigenetic modification by adding lactate to lysine residues on histones. As the research deepens, numerous evidences reveal that lactylation also occurs on non-histone proteins. The discovery of lactylation has expanded our understanding of lactate functions in the pathogenesis of diseases. In this review, we summarize the roles and mechanisms of lactylation in tumor, inflammatory and neural system diseases, in order to provide new ideas for the research, diagnosis and treatment of these diseases.

Keywords

• lactic acid
• lactylation
• tumor
• inflammatory disease
• neural system disease