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Lactylome analysis reveals HADHA lactylation controls energy homeostasis to promote sepsis-induced myocardial depression.

ABSTRACT: Serum lactate levels are interpreted as a marker of tissue hypoxia and often used clinically as an indicator of severity and outcome of patients with sepsis/septic shock. Glycolysis-derived lactate was identified as a substrate for lysine lactylation (Kla), which is a recently described type of posttranslational modification. However, the impact of lactylation on biological processes of sepsis-induced myocardial depression remains largely unknown. Here, we conduct lactylome and proteome profiling, and quantify 1,127 Kla sites, of which 83 are differentially lactated in sepsis-induced myocardial depression. We develop a deep learning-based framework to prioritize the lactylation at K166 and K728 of trifunctional enzyme subunit alpha (HADHA) to be functionally important. We perform validations to show that lactylation of HADHA at K166 and K728 is influenced both by endogenous and exogenous lactate, and further verify that lactylation at K166 and K728 inhibits the activity of HADHA, decreasing ATP production, an

ORGANISM(S): Rattus Rattus

SUBMITTER: Tiening Zhang

PROVIDER: PXD044090 | iProX | Wed Jul 26 00:00:00 BST 2023

REPOSITORIES: iProX

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