MetaboLightsapplication/xmlftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15769/m_MTBLS15769_LC-MS_positive_hilic_v2_maf.tsvftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15769/m_MTBLS15769_LC-MS_negative_hilic_v2_maf.tsvftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15769/a_MTBLS15769_LC-MS_negative_hilic.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15769/i_Investigation.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15769/s_MTBLS15769.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15769/a_MTBLS15769_LC-MS_positive_hilic.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15769/FILES/RAW_FILES/NEG/NTg_4.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15769/FILES/RAW_FILES/POS/NTg_5.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15769/FILES/RAW_FILES/NEG/Mrg15cTg_4.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15769/FILES/RAW_FILES/POS/Mrg15cTg_2.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15769/FILES/RAW_FILES/POS/NTg_1.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15769/FILES/RAW_FILES/POS/QC-1.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15769/FILES/RAW_FILES/POS/NTg_4.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15769/FILES/RAW_FILES/NEG/QC-1.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15769/FILES/RAW_FILES/NEG/Mrg15cTg_3.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15769/FILES/RAW_FILES/NEG/NTg_3.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15769/FILES/RAW_FILES/POS/Mrg15cTg_5.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15769/FILES/RAW_FILES/NEG/NTg_2.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15769/FILES/RAW_FILES/POS/NTg_3.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15769/FILES/RAW_FILES/NEG/QC-2.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15769/FILES/RAW_FILES/POS/Mrg15cTg_1.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15769/FILES/RAW_FILES/NEG/Mrg15cTg_2.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15769/FILES/RAW_FILES/POS/QC-2.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15769/FILES/RAW_FILES/NEG/NTg_5.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15769/FILES/RAW_FILES/POS/Mrg15cTg_4.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15769/FILES/RAW_FILES/NEG/Mrg15cTg_1.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15769/FILES/RAW_FILES/NEG/NTg_1.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15769/FILES/RAW_FILES/NEG/QC-3.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15769/FILES/RAW_FILES/NEG/Mrg15cTg_5.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15769/FILES/RAW_FILES/POS/NTg_2.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15769/FILES/RAW_FILES/POS/QC-3.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15769/FILES/RAW_FILES/POS/Mrg15cTg_3.rawprimaryOK200ftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15769<p>Detected metabolite features were annotated and used for downstream untargeted metabolomics analysis. Processed metabolite data were analyzed using MetaboAnalyst 6.0, and KEGG annotations were used for pathway-based interpretation and enrichment analysis. Differential metabolites were identified using a combination of multivariate and univariate statistical criteria.</p>MetaboLightsPublicLiquid Chromatography MS - positive - hilicLiquid Chromatography MS - negative - hilic<p>Chromatographic separation was performed using a Vanquish UHPLC system (Thermo Fisher Scientific) with hydrophilic interaction chromatography (HILIC). The chromatographic conditions were optimized for broad metabolite profiling prior to high-resolution mass spectrometric detection. Detailed column specifications, mobile-phase gradient, flow rate, column temperature, and injection volume were defined according to the validated analytical method used by the metabolomics service platform.</p>MRG15 orchestrates glycolysis and the pentose phosphate pathway to facilitate heart regeneration following myocardial infarction.Duo KeaiPeking UniversityHeart tissuemass spectrometry assay<p>Frozen heart tissues were extracted using prechilled methanol/acetonitrile/water (2:2:1, v/v/v). Samples were subjected to low-temperature sonication and centrifugation, and the resulting supernatants were dried under vacuum and reconstituted in acetonitrile/water (1:1, v/v) before LC-MS analysis. Pooled quality-control samples were prepared by mixing equal aliquots of individual samples and were injected periodically during the analytical sequence to evaluate instrument stability and analytical reproducibility.</p>Mus musculushttps://www.ebi.ac.uk/metabolights/MTBLS15769Dan Meng. Fudan University. dmeng@fudan.edu.cn.Nan Jiang. Fudan University. 21211010066@m.fudan.edu.cn.<p>Raw LC-MS data were processed to generate a metabolite feature intensity matrix for subsequent statistical analysis. The processed metabolomics data were imported into MetaboAnalyst 6.0 for normalization, multivariate statistical analysis, and differential metabolite analysis. Metabolite intensity data were normalized by sum and auto-scaled before downstream analysis.</p>Groupkeaiduoduo998@126.com<p>Infarcted heart tissues were collected from NTg and Mrg15cTg mice at day 7 after myocardial infarction, with five biological replicates per group. The tissues were immediately snap-frozen in liquid nitrogen and stored at 80°C until metabolomic analysis. Samples from the two groups were collected and processed in parallel to minimize technical variation.</p>MetabolomicsMetabolomicscardiomyocyte proliferationchaperone-mediated autophagyMus musculusHeart tissueMRG15untargeted analysismyocardial infarctionFrozen infarcted heart tissueMetabolic reprogrammingOrbitrap Exploris 480Thermo Scientific Vanquish UHPLC Systemheart regenerationGlycolysispentose phosphate pathway, hexokinase 2Metabolomicscardiomyocyte proliferationchaperone-mediated autophagyMus musculusHeart tissueMRG15untargeted analysismyocardial infarctionFrozen infarcted heart tissueMetabolic reprogrammingOrbitrap Exploris 480Thermo Scientific Vanquish UHPLC Systemheart regenerationGlycolysispentose phosphate pathway, hexokinase 2<p>Mass spectrometric analysis was performed using a Q Exactive Orbitrap mass spectrometer coupled to the Vanquish UHPLC system (Thermo Fisher Scientific). Electrospray ionization was performed in both positive and negative ion modes to achieve broad metabolite coverage. High-resolution mass spectrometric data were acquired for subsequent metabolite feature detection and annotation.</p>TaurineNaringeninPhenylpyruvateAllantoinL-2-hydroxyglutaric acidsn-Glycerol 3-phosphoethanolamineIle-LysProstaglandin f1.alpha.Deoxyinosine3-hydroxy-3-methylglutaric acid3-Phosphoserine3,5-dihydroxybenzoic acidPhosphoenolpyruvateKetoleucineL-Histidine4-(2-hydroxyethyl)piperazine-1-ethanesulfonic acidHexanoylglycineMyristoleic acidPyridoxalIminodiacetic acidSuccinateGlycerolPhenylglyoxylic acid2-hydroxy-3-methylbutyric acidGlycolateL-ProlineCapric acidPhenolDL-tryptophanL-aspartic acidD-myo-inositol-3,4,5,6-tetraphosphateGly-GlyD-galacturonic acid2,3-dihydroxy-3-methylbutyric acidRicinoleic acid2-oleoyl-1-stearoyl-sn-glycero-3-phosphoserineEthyl glucuronidePyrrole-2-carboxylic acidEthyl sulfateGlycineArginineGentisic acidOleic acid21-hydroxyprogesteroneGlutaric acidN-acetyl-l-aspartic acidBeta-hydroxybutyrateD-ribose 1-phosphateInosine 5'-monophosphateCis,cis-muconic acidPentadecanoic acidDopamineL-fucose-1-phosphate1-methyluric acidCinchonineL-theanineLeukotriene d4PseudouridineN-isovaleroylglycineN-acetylneuraminateUridine 5'-diphosphoglucuronic acid6-phosphogluconic acidFumarateDl-a-hydroxybutyric acidD-(+)-galactose7-methyluric acid2-Ethyl-2-Hydroxybutyric acidAnetholeImidaclopridL-ValineUracil2-docosahexaenoyl-1-stearoyl-sn-glycero-3-phosphoserinePantothenic acidEtodolacPGD2Dl-malic acidIndolelactic acid13-hydroxy-9z,11e-octadecadienoic acid2'-deoxyuridine 5'-monophosphateTaurocholate4-pyridoxic acidPristanic acidProstaglandin d1Erucic acidGlyceraldehyde 3-phosphateAllyl isothiocyanateDL-asparagine4'-hydroxychalconeCaprylic acid4-hydroxy-4-methyl-2-pentanone2-mercaptoethanesulfonic acidSuccinic semialdehydeAcetoacetic acidGlyceric acidXanthosine 5'-monophosphateD-sorbitolPhenaceturic acidIsopentenyl pyrophosphatePentanoic acidN-acetyl-l-glutamateL-homocysteic acid3-hydroxyglutaric acidGallic acidCis-4,7,10,13,16,19-docosahexaenoic acidN-formyl-l-methionineArachidonic acid (peroxide free)1-stearoyl-2-arachidonoyl-sn-glycero-3-phosphoserinecis-AconitateL-threonate1-oleoyl-sn-glycero-3-phosphoethanolamineMalateMyristic acid3-Phospho-D-glycerate4-nitrocatecholUridineAdipic acidL-cysteinesulfinic acid12(13)-epoxy-9z-octadecenoic acidD-glutamineMalonic acidHippuric acidAdenosine 5'-diphosphateIndoleD-Glucuronate1-stearoyl-2-linoleoyl-sn-glycero-3-phospho-l-serine.gamma.-hydroxybutyric acidL-homocitrulline3,7-Dimethyluric acidD-AlloseGlycerateIsoleucineEthyl .beta.-d-glucuronide4-nitrophenolCaftaric acidThiouric acidD-fructose 1,6-bisphosphatePyruvateAdenineD-ribulose 5-phosphateN-acetyl-l-tyrosineUric acid6-hydroxyhexanoateN-propyl gallateD-arabinoseLinoleic acidTrans-2,3-dimethylacrylic acid2,4-dichlorophenolHeptadecanoic acidCdp-ethanolamineCitraconic acidInosine2-mercaptobenzothiazoleHypotaurineDL-Glutamic acidDL-threoninePhenylacetic acidCaproic acidN-acetyl-l-methionineGlucosePalmitic acidN-glycolylneuraminic acidCellobiose6-phospho-d-gluconateD-aspartic acidPhosphoric acid3-hydroxymyristic acidPropionic acidPhenylbutazone2-Deoxyribose 5-phosphateNonanoic acid1,3-Dimethyluric acidRibitolLysineN-Acetyl-D-Glucosamine 6-PhosphateO-phosphoethanolamineGlutamic acidP-toluenesulfonic acidTrans-2-hydroxycinnamic acid2,5-furandicarboxylic acidNorharmaneAcetylsalicylic acidPropanoic acidUdp-n-acetylglucosamineAcetyl phosphateN-isobutyrylglycineCreatinine.beta.-glycerophosphateAlanineMyo-inositol1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphocholineAcamprosateXanthosineCyclohexylcarboxylic acidXanthineUridine 5'-monophosphate1,2-benzenedicarboxylic acidValine3,5,6-trichloro-2-pyridinolD-riboseL-gulono-1,4-lactone3-methylthiopropionate1,2-propanediol, 3-(1,3-benzodioxol-5-yl)-Trans-aconitic acidModafinil acidD-mannose-6-phosphate1,2-dioleoyl-sn-glycero-3-phospho-l-serineN-acetylglutamineD-2-phosphoglyceric acidLabetalolD-arabinonic acidInosine 5'-monophosphate (IMP)D-2-aminobutyric acidL-IsoleucineOctadecanoic acidSulfuric acid5-hydroxyindoleacetateL-AlanineMaleic acid(2-aminoethoxy)[2-[docosa-4.7.10.13.16.19-hexaenoyloxy]-3-[hexadec-1-en-1-yloxy]propoxy]phosphinic acidOrotidineIndole-3-acetaldehydeIndoxyl sulfate3-hydroxyoctanoic acid3-hydroxycapric acidCidofovirDehydroascorbic acidCis-7,10,13,16-docosatetraenoic acidIndole-3-butyric acid1,4-butynediolGuanidinopropionic acidL-(+)-lactic acidPyruvaldehydeGuanidinoethyl sulfonatePhosphoserine2-Oxoadipic acidMitragynineButanoic acidD-fructoseDimethylbenzimidazoleN-methyl-l-glutamic acidD-proline7-methylxanthineDodecanoic acid16-hydroxyhexadecanoic acid3,4-dihydroxyhydrocinnamic acidCis-9-palmitoleic acidUridine 5'-diphosphate3,4-dihydroxyacetophenoneD-mannose 6-phosphate3-hydroxydodecanoic acidAzelaic acidHis-serQuinolinateMevalonic acid 5-pyrophosphateL-pyroglutamic acidDL-serineD-mannose 1-phosphate6-HydroxydopamineD-erythronic acid .gamma.-lactoneSedoheptulose 7-phosphateGuanosine 5'-monophosphatePhosphocreatineDodecylbenzenesulfonic acidPyridoxal phosphateLinolenic acidQuinateMaltolVitamin cSarcosineProgesteroneMestranolL-AspartatefalseMRG15 orchestrates glycolysis and the pentose phosphate pathway to facilitate heart regeneration following myocardial infarctionMetabolic 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.2026-09-222026-09-22MTBLS15769HMDB0035213HMDB0062769HMDB0000112HMDB0035422HMDB0038311HMDB0036115HMDB0038361HMDB0000244HMDB0015517HMDB0010407HMDB0011262HMDB0011253HMDB0013122HMDB0036458HMDB0008727HMDB0012108HMDB0000001HMDB0003331HMDB0000898HMDB0010379HMDB0013409HMDB0011149HMDB0008097HMDB0007991HMDB0011503HMDB0010382HMDB0009815HMDB0008057HMDB0010384HMDB0011130HMDB0008039HMDB0000564/HMDB0007878/HMDB0007879/HMDB0007880/HMDB0007882/HMDB0007884/HMDB0007886/HMDB0007887/HMDB0007897/HMDB0007898/HMDB0007911/HMDB0007912/HMDB0007913/HMDB0007914/HMDB0007936/HMDB0007937/HMDB0007938/HMDB0007939/HMDB0007940/HMDB0007958/HMDB0007959/HMDB0007960/HMDB0007961/HMDB0007964/HMDB0007966/HMDB0007967/HMDB0007981/HMDB0007982/HMDB0007983/HMDB0007984/HMDB0007985/HMDB0008002/HMDB0008003/HMDB0008004/HMDB0008005/HMDB0008028/HMDB0008029/HMDB0008065/HMDB0008066/HMDB0008067/HMDB0008068/HMDB0008069/HMDB0008070/HMDB0008071/HMDB0008091/HMDB0008092/HMDB0008119/HMDB0008120/HMDB0008121/HMDB0008126/HMDB0008129/HMDB0008145/HMDB0008147/HMDB0008182/HMDB0008183/HMDB0008186/HMDB0008191/HMDB0008192/HMDB0008230/HMDB0008231/HMDB0008232/HMDB0008233/HMDB0008269/HMDB0008270/HMDB0008271/HMDB0008272/HMDB0008274/HMDB0008304/HMDB0008306/HMDB0008308/HMDB0008309/HMDB0008312/HMDB0008317/HMDB0008322/HMDB0008323/HMDB0008324/HMDB0008375/HMDB0008377/HMDB0008379/HMDB0008400/HMDB0008401/HMDB0008402/HMDB0008409/HMDB0008410/HMDB0008413/HMDB0008414/HMDB0008415/HMDB0008416/HMDB0008426/HMDB0008427/HMDB0008428/HMDB0008429/HMDB0008431/HMDB0008444/HMDB0008507/HMDB0008508/HMDB0008509/HMDB0008510/HMDB0008514/HMDB0008515/HMDB0008516/HMDB0008522/HMDB0008536/HMDB0008537/HMDB0008538/HMDB0008539/HMDB0008540/HMDB0008541/HMDB0008542/HMDB0008543/HMDB0008606/HMDB0008607/HMDB0008608/HMDB0008609/HMDB0008610/HMDB0008611/HMDB0008612/HMDB0008614/HMDB0008615/HMDB0008655/HMDB0008657/HMDB0008658/HMDB0008659/HMDB0008660/HMDB0008661/HMDB0008662/HMDB0008663/HMDB0008664/HMDB0008665/HMDB0008668/HMDB0008669/HMDB0008670/HMDB0008671/HMDB0008672/HMDB0008673/HMDB0008674/HMDB0008676/HMDB0008681/HMDB0008682/HMDB0008683/HMDB0008684/HMDB0008686/HMDB0008688/HMDB0008690/HMDB0008691/HMDB0008692/HMDB0008697/HMDB0008698/HMDB0008699/HMDB0008700/HMDB0008702/HMDB0008703/HMDB0008704/HMDB0008706/HMDB0008707/HMDB0008730/HMDB0008731/HMDB0008732/HMDB0008733/HMDB0008734/HMDB0008735/HMDB0008736/HMDB0008737/HMDB0008738/HMDB0008745/HMDB0008746/HMDB0008747/HMDB0008748/HMDB0008749/HMDB0008750/HMDB0008751/HMDB0008752/HMDB0008754/HMDB0008758/HMDB0008761/HMDB0008762/HMDB0008766/HMDB0008768/HMDB0008770/HMDB0008773/HMDB0008774/HMDB0008775/HMDB0008791/HMDB0008792/HMDB0008793/HMDB0008795/HMDB0008796/HMDB0008798/HMDB0008799/HMDB0008800HMDB0008206HMDB0008443HMDB0008138HMDB0009093HMDB0062690HMDB0007934HMDB0013674HMDB0013675HMDB0000640HMDB0002059HMDB0012535HMDB0001065HMDB0004666HMDB0008946HMDB0000617HMDB0015497HMDB0000338HMDB0001864HMDB0008928HMDB0011538HMDB0007972HMDB0140912HMDB0041799HMDB0000905HMDB0000014HMDB0000071HMDB0029646HMDB0013751HMDB0032039HMDB0012154HMDB0001476HMDB0062735HMDB0000754HMDB0000479HMDB0015506HMDB0001538HMDB0000026HMDB0032616HMDB0001392HMDB0001169HMDB0060287HMDB0015344HMDB0032985HMDB0003192HMDB0001149HMDB0003355HMDB0006248HMDB0000079HMDB0000982HMDB0002894HMDB0001517HMDB0002886HMDB0000897HMDB0001107HMDB0004679HMDB0004669HMDB0062179HMDB0001859HMDB0000895HMDB0000050HMDB0003540HMDB0000061HMDB0000045HMDB0000536HMDB0006552HMDB0035208HMDB0004350HMDB0004484HMDB0003012HMDB0000194HMDB0031342HMDB0030352HMDB0000052HMDB0035782HMDB0000168HMDB0033850HMDB0015249HMDB0033249HMDB0014857HMDB0014352HMDB0013609HMDB0034413HMDB0002835HMDB0003119HMDB0013679HMDB0000043HMDB0000030HMDB0014382HMDB0125102HMDB0014704HMDB0031769HMDB0014500HMDB0000097HMDB0012199HMDB0002068HMDB0041857HMDB0015043HMDB0012915HMDB0000064HMDB0031817HMDB0031404HMDB0000089HMDB0001413HMDB0000095HMDB0001176HMDB0000630HMDB0033780HMDB0001321HMDB0000124HMDB0001254HMDB0001401HMDB0003374HMDB0060254HMDB0004231HMDB0003407HMDB0036491HMDB0033244HMDB0014628HMDB0094660HMDB0131138HMDB0001473HMDB0002151HMDB0000092HMDB0014425HMDB0014960HMDB0033923HMDB0000162HMDB0000158HMDB0000883HMDB0005056HMDB0003045HMDB0126018HMDB0005030HMDB0001520HMDB0033704HMDB0011737HMDB0035830HMDB0001586HMDB0000125HMDB0003337HMDB0000126HMDB0000086HMDB0000138HMDB0000132HMDB0030311HMDB0061822HMDB0000756HMDB0000133HMDB0000870HMDB0000177HMDB0060949HMDB0000725/HMDB0036576HMDB0000157HMDB0029739HMDB0001873HMDB0000736HMDB0032348HMDB0037316HMDB0031195HMDB0034312HMDB0031797HMDB0015197HMDB0000704HMDB0000646HMDB0002706HMDB0062496HMDB0000033HMDB0000904HMDB0000148HMDB0000641HMDB0000670HMDB0000719HMDB0000696HMDB0013716HMDB0000070/HMDB0000716HMDB0062514HMDB0062698HMDB0000167HMDB0000929HMDB0005008HMDB0032358HMDB0015141HMDB0000687HMDB0006469HMDB0000761HMDB0001296HMDB0034666HMDB0036089HMDB0014597HMDB0000749HMDB0240285HMDB0014693HMDB0001522HMDB0014523HMDB0014380HMDB0000858HMDB0005066HMDB0003357HMDB0001348HMDB0002372HMDB0000212HMDB0000215HMDB0001129HMDB0013253HMDB0014748HMDB0000230HMDB0002201HMDB0013866HMDB0012107HMDB0031419HMDB00121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