Genes & diseasesSep 17, 2026

Lactylation's role in metabolism, gene control, and cell death in heart tissue damage after blood flow returns

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Sep 18, 2026

Abstract

Histone lysine lactylation (Kla) may play a significant role in myocardial ischemia/reperfusion injury (MI/RI).

Myocardial ischemia/reperfusion injury is associated with various cell death pathways including autophagy, apoptosis, pyroptosis, and ferroptosis.
Lactate influences cardiac energy metabolism and is linked to modifications such as acetylation, phosphorylation, and ubiquitination.
Kla exhibits a dual regulatory function in MI/RI, interacting with traditional post-translational modifications.
Targeting lactate-related molecules like lactate dehydrogenase A (LDHA) and monocarboxylate transporters (MCTs) could have therapeutic potential.
Exploring dynamic patterns of Kla may lead to new therapeutic targets for preventing and treating MI/RI.

Simplified

One important pathogenic process that contributes to subsequent damage after myocardial infarction (MI) revascularization is myocardial ischemia/reperfusion injury (MI/RI). Its underlying mechanisms are controlled by traditional post-translational modifications (PTMs) like acetylation, methylation, phosphorylation, and ubiquitination, and involve several cell death pathways, such as autophagy, apoptosis, pyroptosis, and ferroptosis. Histone lysine lactylation (Kla), a novel metabolically related epigenetic regulation mechanism, has attracted a lot of attention in recent years. This review systematically clarifies the crucial role of lactate in cardiac energy metabolism and its influence on Kla modification, exploring Kla's dual regulatory function in MI/RI. It demonstrates a significant interaction between Kla and changes like acetylation, phosphorylation, N6-methyladenosine (m6A) methylation, and ubiquitination, thereby establishing putative connections that regulate cell death in MI/RI. Targeting lactate-related molecules such as lactate dehydrogenase A (LDHA), monocarboxylate transporters (MCTs), and histone deacetylases (HDACs) shows therapeutic potential. Therefore, targeted intervention molecules applicable at different stages of MI/RI are explored. Ultimately, elucidating the dynamic patterns of Kla and its crucial involvement in various biological processes will create new paradigms and potential therapeutic targets for the prevention and treatment of MI/RI.

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Lactylation's role in metabolism, gene control, and cell death in heart tissue damage after blood flow returns

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