Table 2.
List of lactylation events that regulate lipid metabolism.
| Substrates | Lactylation sites | Writer/Eraser | Functions | Health/disease | Refs |
|---|---|---|---|---|---|
| FASN | K528/673/1071 | / | Modulates the MAT domain by lactylation, thereby suppressing FASN enzymatic activity and consequently reducing DNL | NAFLD, HCC, HIIT | [33–35] |
| APOC2 | K70 | P300/HADC3 | Induces immunotherapy resistance by promoting extracellular lipolysis | NSCLC | [32] |
| CPT2 | K457/458 | AARS2/SIRT3 | Integrates intracellular hypoxia and lactate to regulate OXPHOS, and induces follicle development | Exercise, POI | [37, 57] |
| SPRING | K82 | KAT7 | pAKT/pPCK1/pLDHA/SPRINGla axis induces ferroptosis resistance in AKT-hyperactivated ICC via MVA flux reprogramming. | ICC | [83] |
| HADHA | K519, K415, K644, K60, and K569 | / | KDM6B-mediated HADHA demethylation/lactylation promotes FAO and mineralization | Periodontitis | [62] |
| HADHA | K166, K728 | SIRT1/3 | Disturbs cardiomyocyte mitochondrial function and energy metabolism | Septic myocardial depression | [65] |
| PCK2 | K100 | KAT8 | Aggravates hepatic ferroptosis during IRI by OXSM-dependent mtFAS reprogramming | LT | [44] |
| Histone H3 | K18 | / | Promotes HCC via lipid metabolism remodeling | HCC | [45] |
| Histone H3 | K18 | / | PPARα activation reverses acquired resistance to TMZ in GBM by inhibiting H3K18la | GBM | [61] |
| Histone H3 | K12 | / | H4k12la mediated by Fam172a in POMC neurons regulates lipid and glucose metabolism | Obesity | [49] |
| Histone H3 | K18 | P300 | H3K18la-induced ACAT2/sEV-cholesterol axis orchestrates cholesterol-mediated immunosuppressive reprogramming | PC | [84] |
| Histone H3 | K18 | / | Promotes NAFLD via targeting METTL3/YTHDF1/SCD1 m6A axis | NAFLD | [48] |
| Histone H3 | K18 | / | Activates HIF1A and exacerbates SAP via ACSL4/LPCAT3/ALOX15 pathway-induced ferroptosis | SAP | [74] |
| Histone H3 | K18 | P300/CBP | H3K18la-driven mechanism induces ferroptosis via METTL3-mediated m6A modification | ALI | [72] |
| Histone H3 | K18 | P300/CBP/SIRT3 | Induces ACSL4 transcription to activate ferroptosis | IVDD | [73] |
| GCLM | K34 | ACAT2 | Promotes ferroptosis resistance in KRASG12D-mutant cancers | KRASG12D mutant cancers | [86] |
| Histone H3 | K18 | / | Induces hCG-induced luteinization in hypoxic GCs by upregulating CYP11A1 and STAR transcription | Luteal insufficiency | [85] |
| Histone H3 | K18 | / | Induces chondrocyte ferroptosis | OA | [135] |
| ACSL4 | K412 | P300/CBP/SIRT3 | Activates ferroptosis | IVDD | [73] |
| ARF1 | K73 | / | Promotes LRP1-induced mitochondria release in astrocyte–neuron crosstalk | Stroke | [143] |
| NSUN2 | K508 | NAA10 | Drives cancer resistance to ferroptosis by enhancing GCLC/GSH signaling | GC | [75] |
| Vps34 | K356/K781 | KAT5/TIP60 | Increases lipid kinase activity and promotes autophagic flux and endolysosomal trafficking | Exercise, Cancer | [76] |
| RUBCN | K33 | / | Promotes PI3P levels and LAP formation via interaction with Vps34 | Infectious diseases | [78] |
| APOA4, APOC1, APOC3 | / | / | Promotes downregulation of cholesterol-related proteins | Tendinopathy | [93] |
| Histone H4 | K12 | / | Promotes chemotherapy resistance by regulating ABCC2, ABCC3, and ABCC10 | DLCC | [95] |
| Histone H3 | K18 | / | H3k18la-driven GPD2 regulates M2 polarization to induce metastasis of CC | CC | [79] |
| MeCP2 | K271 | P300/HDAC3 | Exercise-induced Mecp2 lactylation alleviates atherosclerosis | Atherosclerosis | [121, 124] |
| Histone H3 | K18 | P300/HADC3 | Promotes lipid peroxidation-induced EndMT and increases lipid burden with P300/ASF1A molecular complex | Atherosclerosis | [122] |
| Histone H4 | K12 | HADC3 | Promotes atherosclerosis by TRAP1-induced metabolic reprogramming | Atherosclerosis | [125] |
| PCSK9 | Pan-Kla | / | Promotes progression and metastasis of colon cancer | Colon cancer | [94] |
| AMPKα | / | / | Exacerbates NPC senescence | IVDD | [134] |
| HADHB | K273 | / | Regulates FA metabolism in mice liver | Exercise | [66] |
| ACSL1 | K676 | / | Promotes FA metabolism and fat loss | Exercise | [66] |