Targeted metabolites were identified based on their characteristic precursor and product ion transitions and chromatographic behavior in MRM analysis. Metabolite identities were assigned using authentic reference standards and corresponding metabolite information, including HMDB identifiers where available. Quantification was performed using calibration curves and isotope-labeled internal standards.
"],"repository":["MetaboLights"],"study_status":["Public"],"ptm_modification":[""],"instrument_platform":["Liquid Chromatography MS - alternating - hilic","Liquid Chromatography MS - alternating - reverse-phase"],"chromatography_protocol":["Targeted metabolites were separated using an Agilent 1290 Infinity II UHPLC system. Reverse-phase chromatography was performed using an ACQUITY UPLC BEH C18 column (1.7 μm, 2.1 mm × 150 mm), while hydrophilic interaction chromatography was performed using an Atlantis Premier BEH Z-HILIC column (1.7 μm, 2.1 mm × 150 mm). For reverse-phase chromatography, mobile phase A was water containing 0.1% formic acid, and mobile phase B was methanol/water (95:5, v/v) containing 10 mM ammonium formate. For HILIC chromatography, mobile phase A was water/acetonitrile (90:10, v/v) containing 10 mM ammonium acetate, and mobile phase B was water/acetonitrile (10:90, v/v) containing 10 mM ammonium acetate. The autosampler temperature was maintained at 6°C, and the injection volume was 2 μL.
"],"publication":["MRG15 orchestrates glycolysis and the pentose phosphate pathway to facilitate heart regeneration following myocardial infarction."],"submitter_affiliation":["Peking University"],"submitter_name":["Duo Keai"],"organism_part":["Heart"],"technology_type":["mass spectrometry assay"],"disease":[""],"extraction_protocol":["Approximately 25 mg of frozen heart tissue was extracted with 500 μL methanol/water (4:1, v/v) containing internal standards. Samples were homogenized at 40 Hz for 4 min, sonicated in an ice-water bath for 5 min, and the homogenization/sonication cycle was repeated three times. Samples were then incubated at 40°C for 1 h and centrifuged at 12,000 rpm for 15 min at 4°C, and the supernatants were collected for LC-MS analysis. Calibration standards containing isotope-labeled internal standards were prepared for metabolite quantification.
"],"organism":["Mus musculus"],"full_dataset_link":["https://www.ebi.ac.uk/metabolights/MTBLS15770"],"author":["Dan Meng. Fudan University. dmeng@fudan.edu.cn.","Nan Jiang. Fudan University. 21211010066@m.fudan.edu.cn."],"data_transformation_protocol":["Raw targeted metabolomics data were acquired using SCIEX Analyst Work Station Software, version 1.7.3. MRM data were processed and quantified using BioBud, version 2.0.4. Metabolite concentrations were calculated from calibration curves using the corresponding internal standards and normalized to tissue weight.
"],"study_factor":["Group"],"submitter_email":["keaiduoduo998@126.com"],"sample_collection_protocol":["Infarcted heart tissues were collected from NTg and Mrg15cTg mice at day 7 post-myocardial infarction, with four biological replicates per group. Tissues were immediately frozen and stored at 80°C until metabolomic analysis. Samples were processed in parallel for targeted metabolomic analysis.
"],"omics_type":["Metabolomics"],"study_design":["Heart","Metabolomics","Mus musculus","cardiomyocyte proliferation","chaperone-mediated autophagy","targeted analysis","hexokinase 2","MRG15","myocardial infarction","Metabolic Reprogramming","pentose phosphate pathway","Infarcted heart tissue","AB SCIEX Triple Quad 6500+","heart regeneration","Glycolysis","Agilent 1290 Infinity II UHPLC"],"curator_keywords":["Heart","Metabolomics","Mus musculus","cardiomyocyte proliferation","chaperone-mediated autophagy","targeted analysis","hexokinase 2","MRG15","myocardial infarction","Metabolic Reprogramming","pentose phosphate pathway","Infarcted heart tissue","AB SCIEX Triple Quad 6500+","heart regeneration","Glycolysis","Agilent 1290 Infinity II UHPLC"],"mass_spectrometry_protocol":["Mass spectrometric analysis was performed using a SCIEX Triple Quad 6500+ mass spectrometer equipped with an IonDrive Turbo V electrospray ionization source. Targeted metabolites were analyzed in multiple reaction monitoring (MRM) mode using both positive and negative ionization modes. The IonSpray voltage was set to +5500 V in positive mode and 4500 V in negative mode, with a source temperature of 400°C. Curtain gas was set to 35 psi, while Ion Source Gas 1 and Gas 2 were each set to 50 psi.
"],"metabolite_name":["D-Fructose","Succinyl-CoA","Dihydronicotinamide adenine dinucleotide phosphate","Glycolic Acid","D-Ribulose 5-phosphate","Glucaric acid","Uridine-5'-diphosphate","Guanosine-5'-triphosphate","Glyceraldehyde 3-phosphate","Mannose 6-phosphate","Adenosine 5'-diphosphoribose","Erythrose 4-phosphate","Itaconic acid","Orotic acid","Thymidine-5'-phosphate","Glycerophosphoric acid","Methylmalonic acid","Uridine diphosphate glucose","Ribose-5-Phosphate","Maleic acid","Malic acid","Succinic semialdehyde","3-Phosphoglyceric acid","Glyceric acid","Flavin adenine dinucleotide","6-phosphogluconolactone","alpha-Ketoglutaric acid","2-Oxobutanoic acid","Gluconic acid","3',5'-cyclic AMP","L-Cystine","3-Ureidopropionic acid","alpha-Ketoisovaleric acid","Guanosine Diphosphate-Fucose","Vanillylmandelic acid","Glucose-1-phosphate","2-Phosphoglyceric acid","D-Glucuronic acid","Guanosine Diphosphate-Mannose","Uridine-5'-monophosphate","Oxalic acid","Oxalacetic acid","Fructose-1,6-diphosphate","Uridine","Succinic acid","Trehalose-6-phosphate","D-Glucose","2-Oxoadipic acid","N-Acetylglucosamine 6-phosphate","Hippuric acid","D-Glucose-6-phosphate","Guanosine-5'-diphosphate","Pyruvic acid","L-Cysteic acid","4-Hydroxyphenylpyruvic acid","Ribulose 1,5-bisphosphate","Isocitric acid","Mevalonic acid","UDP-N-acetylglucosamine","Coenzyme A","2-Aminobenzoic acid","L-Lactic acid","Quinolinic acid","2-Hydroxybutyric acid","cis-Aconitic acid","Glucosamine 6-phosphate","Deoxyuridine monophosphate","Fructose-6-phosphate","Adenosine-5'-triphosphate","Phosphoenolpyruvic acid","Indole-3-acetic acid","Sedoheptulose 7-phosphate","1,4-Dihydronicotinamide adenine dinucleotide","Phosphoribosyl pyrophosphate","3-Hydroxypropionic acid","2-Hydroxyglutaric acid","6-Phosphogluconic acid","Citric acid","Homogentisic acid","N-Acetylglucosamine 1-phosphate","D-Ribose","Adenosine-5'-diphosphate","Uridine diphosphate glucuronic acid","Fumaric acid","Citraconic acid","Inosine","Trans-Aconitic acid","Glutaryl-CoA","Uracil","3-Hydroxybutyric acid"],"additional_accession":[]},"is_claimable":false,"name":"MRG15 orchestrates glycolysis and the pentose phosphate pathway to facilitate heart regeneration following myocardial infarction","description":"Metabolic reprogramming is crucial for adult heart regeneration after myocardial infarction (MI). Here, we identify the MORF4-related gene on chromosome 15 (MRG15) as a key orchestrator of cardiomyocyte metabolism to drive cardiomyocyte proliferation. MRG15 expression is upregulated in both hypoxic cardiomyocytes and infarcted human and mouse hearts. Cardiomyocyte-specific Mrg15 overexpression enhances glycolysis and the pentose phosphate pathway (PPP), promoting cardiomyocyte proliferation and cardiac function restoration after MI, whereas Mrg15 deficiency impairs heart regeneration. Mechanistically, cytoplasmic MRG15 interacts with hexokinase 2 (HK2) and enhances its protein stability by preventing its chaperone-mediated autophagy (CMA)-dependent degradation, which requires MRG15 residues 141–145. MRG15-mediated stabilization of HK2 orchestrates glycolysis and PPP, thereby facilitating cardiomyocyte proliferation and heart regeneration in adult mice post-MI. Our results underscore the importance of MRG15-mediated metabolic reprogramming in heart regeneration. By fine-tuning the activity of glycolysis and PPP, MRG15 represents a compelling therapeutic target for regenerative interventions following ischemic injury.","dates":{"publication":"2026-09-22","submission":"2026-09-22"},"accession":"MTBLS15770","cross_references":{"HMDB":["HMDB0000125","HMDB0003337","HMDB0000052","HMDB0002243","HMDB0001206","HMDB0001294","HMDB0001514","HMDB0000230","HMDB0000855","HMDB0000217","HMDB0000050","HMDB0000045","HMDB0000939","HMDB0001185","HMDB0000133","HMDB0001397","HMDB0001520","HMDB0000902","HMDB0000905","HMDB0000229","HMDB0000161","HMDB0000191","HMDB0000112","HMDB0000148","HMDB0000641","HMDB0000123","HMDB0000696","HMDB0000162","HMDB0000187","HMDB0000267","HMDB0000517","HMDB0000159","HMDB0000883","HMDB0000167","HMDB0000574","HMDB0000687","HMDB0000172","HMDB0000214","HMDB0000168","HMDB0000182","HMDB0000177","HMDB0000929","HMDB0000158","HMDB0000904","HMDB0000064","HMDB0000562","HMDB0000092","HMDB0001372","HMDB0000034","HMDB0000132","HMDB0000157","HMDB0000630","HMDB0000962","HMDB0000043","HMDB0000097","HMDB0001406","HMDB0000094","HMDB0000072","HMDB0000193","HMDB0000208","HMDB0000254","HMDB0000134","HMDB0000156","HMDB0000263","HMDB0000243","HMDB0000190","HMDB0059655","HMDB0000202","HMDB0000176","HMDB0341410","HMDB0000005","HMDB0000011","HMDB0000634","HMDB0000115","HMDB0000700","HMDB0002092","HMDB0002329","HMDB0001259","HMDB0001123","HMDB0000019","HMDB0000226","HMDB0000225","HMDB0000227","HMDB0000130","HMDB0000707","HMDB0000026","HMDB0000232","HMDB0000291","HMDB0000958","HMDB0000223","HMDB0000126","HMDB0001548","HMDB0000618","HMDB0258206","HMDB0001321","HMDB0001127","HMDB0001316","HMDB0000122","HMDB0001586","HMDB0001401","HMDB0000124","HMDB0001058","HMDB0001112","HMDB0000807","HMDB0000362","HMDB0001078","HMDB0000660","HMDB0000139","HMDB0000625","HMDB0000663","HMDB0000280","HMDB0001124","HMDB0001254","HMDB0001367","HMDB0002817","HMDB0000283","HMDB0000127","HMDB0304322","HMDB0001487","HMDB0001341","HMDB0000538","HMDB0000058","HMDB0001248","HMDB0001201","HMDB0001273","HMDB0000296","HMDB0000288","HMDB0000295","HMDB0000195","HMDB0001227","HMDB0000300","HMDB0000286","HMDB0001423","HMDB0001409","HMDB0001178","HMDB0000290","HMDB0001163","HMDB0252660","HMDB0000714","HMDB0000192","HMDB0002757","HMDB0001022","HMDB0000221","HMDB0001339","HMDB0000935","HMDB0000197"]}}