2016
Mitochondrial Reactive Oxygen Species Mediate Cardiac Structural, Functional, and Mitochondrial Consequences of Diet‐Induced Metabolic Heart Disease
Sverdlov AL, Elezaby A, Qin F, Behring JB, Luptak I, Calamaras TD, Siwik DA, Miller EJ, Liesa M, Shirihai OS, Pimentel DR, Cohen RA, Bachschmid MM, Colucci WS. Mitochondrial Reactive Oxygen Species Mediate Cardiac Structural, Functional, and Mitochondrial Consequences of Diet‐Induced Metabolic Heart Disease. Journal Of The American Heart Association 2016, 5: e002555. PMID: 26755553, PMCID: PMC4859372, DOI: 10.1161/jaha.115.002555.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsCatalaseDiet, High-FatDietary SucroseDisease Models, AnimalElectron Transport Complex IElectron Transport Complex IIEnergy MetabolismHypertrophy, Left VentricularMice, Inbred C57BLMice, TransgenicMitochondria, HeartMitochondrial DiseasesMutationOxidation-ReductionOxidative StressProtein Processing, Post-TranslationalReactive Oxygen SpeciesVentricular Dysfunction, LeftVentricular Function, LeftConceptsOxidative posttranslational modificationsMitochondrial reactive oxygen speciesPosttranslational modificationsReactive oxygen speciesMetabolic heart diseaseATP synthesisMitochondrial dysfunctionCardiac mitochondrial proteinsSite-directed mutationsMitochondrial proteinsTransgenic miceWild-type miceComplex IMitochondriaMitochondrial abnormalitiesHigh palmitateOxygen speciesCardiac mitochondriaCys100Mitochondrial consequencesCys103Key mediatorProteinH2O2 productionHigh-fat high-sucrose diet
2015
Partial Liver Kinase B1 (LKB1) Deficiency Promotes Diastolic Dysfunction, De Novo Systolic Dysfunction, Apoptosis, and Mitochondrial Dysfunction With Dietary Metabolic Challenge
Miller EJ, Calamaras T, Elezaby A, Sverdlov A, Qin F, Luptak I, Wang K, Sun X, Vijay A, Croteau D, Bachschmid M, Cohen RA, Walsh K, Colucci WS. Partial Liver Kinase B1 (LKB1) Deficiency Promotes Diastolic Dysfunction, De Novo Systolic Dysfunction, Apoptosis, and Mitochondrial Dysfunction With Dietary Metabolic Challenge. Journal Of The American Heart Association 2015, 5: e002277. PMID: 26722122, PMCID: PMC4859355, DOI: 10.1161/jaha.115.002277.Peer-Reviewed Original ResearchMeSH KeywordsAMP-Activated Protein KinasesAnimalsApoptosisApoptosis Regulatory ProteinsCaspase 3DiastoleDiet, High-FatDietary SucroseDisease Models, AnimalGenetic Predisposition to DiseaseHeterozygoteHypertrophy, Left VentricularMice, KnockoutMitochondria, HeartMyocardiumPhenotypeProtein Serine-Threonine KinasesSignal TransductionSystoleTime FactorsTumor Suppressor Protein p53Tumor Suppressor ProteinsVentricular Dysfunction, LeftVentricular Function, LeftVentricular RemodelingConceptsHigh-sucrose dietSystolic dysfunctionDiastolic dysfunctionLiver kinase B1Metabolic heart diseaseDietary excessHeart diseaseMyocardial hypertrophyDe novo appearanceControl dietRestrictive filling patternSevere diastolic dysfunctionLeft ventricular dilationMitochondrial dysfunctionMetabolic stressWild-type miceHigh-sucrose feedingNovo appearanceP53/PUMAMore hypertrophyDiastolic functionMyocardial dysfunctionVentricular hypertrophyVentricular dilationSevere mitochondrial dysfunction
2014
Mitochondrial remodeling in mice with cardiomyocyte-specific lipid overload
Elezaby A, Sverdlov AL, Tu VH, Soni K, Luptak I, Qin F, Liesa M, Shirihai OS, Rimer J, Schaffer JE, Colucci WS, Miller EJ. Mitochondrial remodeling in mice with cardiomyocyte-specific lipid overload. Journal Of Molecular And Cellular Cardiology 2014, 79: 275-283. PMID: 25497302, PMCID: PMC4301992, DOI: 10.1016/j.yjmcc.2014.12.001.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsCarnitineCatalaseCeramidesCyclic AMP Response Element-Binding ProteinDiglyceridesElectron Transport Complex IIFatty Acid Transport ProteinsGene Expression RegulationHydrogen PeroxideLipidsMiceMitochondria, HeartModels, BiologicalMyocardiumMyocytes, CardiacOrgan SpecificityOxygen ConsumptionPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaPhosphorylationPPAR alphaProtein Kinase CProto-Oncogene Proteins c-aktRNA, MessengerSphingomyelinsTranscription FactorsConceptsMetabolic heart diseaseMitochondrial structureMitochondrial fusion genes Mfn1Mitochondrial-targeted catalaseOverexpression of catalaseMitochondrial oxidative stressStructure/functionPhosphorylation of AktToxic metabolite accumulationTranscriptional regulationMitochondrial structure/functionFatty acid uptakeCardiomyocyte lipid accumulationMitochondrial remodelingMetabolite accumulationDiacylglycerol speciesExcess FAATP synthesisMitochondrial functionMitochondrial dysfunctionLipid speciesFA uptakeMitochondrial sizeHydrogen peroxide productionSubunit BHigh fat, high sucrose diet causes cardiac mitochondrial dysfunction due in part to oxidative post-translational modification of mitochondrial complex II
Sverdlov AL, Elezaby A, Behring JB, Bachschmid MM, Luptak I, Tu VH, Siwik DA, Miller EJ, Liesa M, Shirihai OS, Pimentel DR, Cohen RA, Colucci WS. High fat, high sucrose diet causes cardiac mitochondrial dysfunction due in part to oxidative post-translational modification of mitochondrial complex II. Journal Of Molecular And Cellular Cardiology 2014, 78: 165-173. PMID: 25109264, PMCID: PMC4268348, DOI: 10.1016/j.yjmcc.2014.07.018.Peer-Reviewed Original ResearchConceptsCysteine oxidative post-translational modificationsOxidative post-translational modificationsCardiac mitochondrial proteinsPost-translational modificationsMetabolic heart diseaseMitochondrial proteinsATP synthesisMitochondrial dysfunctionBasic Mitochondrial BiologyCardiac mitochondriaMitochondrial biologyOxidative stressTag labelingCardiac mitochondrial dysfunctionBiotin switchSubunit AATP productionMitochondrial ROSGSH/GSSG ratioFunctional consequencesMitochondriaReversible oxidationGSSG ratioProteinSDHA