Lactate exhibits various biological functions, including the mediation of histone and non-histone lactylation to regulate gene transcription, influencing the activity of T lymphocytes, NK cells, and macrophages in immune suppression, activating G protein-coupled receptor 81 for signal transduction, and serving as an energy substrate. The m
6
A modification represents the most prevalent post-transcriptional epigenetic alteration. It is regulated by m
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A-related regulatory enzymes (including methyltransferases, demethylases, and recognition proteins) that control the transcription, splicing, stability, and translation of downstream target RNAs. Lactate-mediated lactylation at histone H3K18 can modulate downstream target m
6
A modifications by enhancing the transcriptional expression levels of m
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A-related regulatory enzymes. These enzymes play a crucial role in the progression of diseases such as cancer, fibrosis (in both liver and lung), myocardial ischemia, cerebral hemorrhage, and sepsis. Furthermore, m
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A-related regulatory enzymes are also subject to lactylation by lactate. In turn, these regulatory enzymes can influence key glycolytic pathway enzymes or modify lactate transporter MCT4 via m
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A alterations to impact lactate levels and subsequently affect lactylation processes.
Graphical abstract
1. Lactate exhibits various biological functions, including the mediation of histone and non-histone lactylation, immune suppression, activating signal transduction, and serving as an energy substrate.
2. Lactate-induced lactylation of histone or non-histone can regulate downstream targets by influencing the transcription and activity of m
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A-RRE.
3. m
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A-RRE-mediated modifications can affect key enzymes in the glycolytic pathway or MCT4, impacting lactate levels.
