2024
Mitochondrial network remodeling of the diabetic heart: implications to ischemia related cardiac dysfunction
Rudokas M, McKay M, Toksoy Z, Eisen J, Bögner M, Young L, Akar F. Mitochondrial network remodeling of the diabetic heart: implications to ischemia related cardiac dysfunction. Cardiovascular Diabetology 2024, 23: 261. PMID: 39026280, PMCID: PMC11264840, DOI: 10.1186/s12933-024-02357-1.Peer-Reviewed Original ResearchConceptsReactive oxygen speciesMitochondrial network remodelingDamaged mitochondrial DNAEfficiency of oxidative phosphorylationImpaired ATP productionMitochondrial ultrastructural alterationsCardiac functionDiabetic heartCellular energy metabolismProduction of reactive oxygen speciesMitochondrial DNAMitochondrial networkMitochondrial fissionExcessive production of reactive oxygen speciesOxidative phosphorylationATP productionResponse to ischemic insultGlobal cardiac functionCell deathOverall cardiac functionCardiac ischemic injuryResponse to injuryCardiac mitochondriaIrreversible cell deathMitochondria
2018
The Mitochondrial Translocator Protein and the Emerging Link Between Oxidative Stress and Arrhythmias in the Diabetic Heart
Ilkan Z, Akar FG. The Mitochondrial Translocator Protein and the Emerging Link Between Oxidative Stress and Arrhythmias in the Diabetic Heart. Frontiers In Physiology 2018, 9: 1518. PMID: 30416455, PMCID: PMC6212558, DOI: 10.3389/fphys.2018.01518.Peer-Reviewed Original Research
2015
The Mitochondrial Translocator Protein and Arrhythmogenesis in Ischemic Heart Disease
Motloch LJ, Hu J, Akar FG. The Mitochondrial Translocator Protein and Arrhythmogenesis in Ischemic Heart Disease. Oxidative Medicine And Cellular Longevity 2015, 2015: 234104. PMID: 25918579, PMCID: PMC4397036, DOI: 10.1155/2015/234104.Peer-Reviewed Original ResearchConceptsIschemic heart diseaseHeart diseaseTranslocator proteinAcute ischemia-reperfusion injuryReactive oxygen speciesIschemia-reperfusion injuryMultiple organ systemsExcitation-contraction couplingMultiple cardiovascular disordersPermeability transition poreRole of TSPOMyocardial infarctionInflammatory processDiverse pathophysiological processesImmune responseCardiovascular disordersTherapeutic targetPathophysiological processesOrgan systemsDiagnostic markerMitochondrial dysfunctionDiseaseAbundant expressionMitochondrial translocator proteinROS release
2013
TAT-HKII induced reduction in mitochondrial bound hexokinase II increases ischemia reperfusion injury by increased respiration and increased ROS levels
Nederlof R, Guerel E, Xie C, Eerbeek O, Koeman A, Hollmann M, Southworth R, Akar F, Mik E, Zuurbier C. TAT-HKII induced reduction in mitochondrial bound hexokinase II increases ischemia reperfusion injury by increased respiration and increased ROS levels. European Heart Journal 2013, 34: 3694. DOI: 10.1093/eurheartj/eht309.3694.Peer-Reviewed Original ResearchMitochondrial oxygen tensionPeptide treatmentReperfusion injuryCardiac functionLDH activityROS productionControl groupHexokinase IIIschemia/reperfusion injuryOxygen consumptionIschemia-reperfusion injuryReactive oxygen speciesOxygen tensionCardiac oxygen consumptionCell deathBorderline ischemiaReperfusion necrosisR damageMin reperfusionReversible ischemiaIrreversible ischemiaMin ischemiaIschemiaTreatment groupsReperfusion
2012
GSH or Palmitate Preserves Mitochondrial Energetic/Redox Balance, Preventing Mechanical Dysfunction in Metabolically Challenged Myocytes/Hearts From Type 2 Diabetic Mice
Tocchetti CG, Caceres V, Stanley BA, Xie C, Shi S, Watson WH, O’Rourke B, Spadari-Bratfisch RC, Cortassa S, Akar FG, Paolocci N, Aon MA. GSH or Palmitate Preserves Mitochondrial Energetic/Redox Balance, Preventing Mechanical Dysfunction in Metabolically Challenged Myocytes/Hearts From Type 2 Diabetic Mice. Diabetes 2012, 61: 3094-3105. PMID: 22807033, PMCID: PMC3501888, DOI: 10.2337/db12-0072.Peer-Reviewed Original ResearchConceptsMechanical dysfunctionReactive oxygen speciesType 2 diabetic db/db miceDiabetic db/db miceHigh glucoseType 2 diabetic patientsType 2 diabetic miceDb/db miceLower cardiac performanceLimited exercise capacityPoor glycemic controlType 2 diabetesΒ-agonist isoproterenolCardiac work demandsFatty acid palmitateExercise capacitySympathetic driveGlycemic controlDiabetic patientsDiabetic miceDb miceHeart dysfunctionPatient's inabilityMitochondrial reactive oxygen speciesHeart preparation
2011
Biophysical properties and functional consequences of reactive oxygen species (ROS)‐induced ROS release in intact myocardium
Biary N, Xie C, Kauffman J, Akar FG. Biophysical properties and functional consequences of reactive oxygen species (ROS)‐induced ROS release in intact myocardium. The Journal Of Physiology 2011, 589: 5167-5179. PMID: 21825030, PMCID: PMC3225672, DOI: 10.1113/jphysiol.2011.214239.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntioxidantsArrhythmias, CardiacCyclosporineDiazepamEthidiumFluorescenceFluorescent DyesHydrogen PeroxideIn Vitro TechniquesIntracellular MembranesMitochondrial Membrane Transport ProteinsMitochondrial Permeability Transition PoreMyocardiumOrganometallic CompoundsOxidantsOxidative StressRatsSalicylatesSuperoxidesVoltage-Dependent Anion ChannelsConceptsIncidence of arrhythmiasIntact myocardiumOxidative stressMitochondrial permeability transition poreReactive oxygen speciesSustained ventricular tachycardiaROS releaseExposure of heartsGlobal oxidative stressPerfusion of heartsSuperoxide dismutase/catalase mimetic EUK-134Functional consequencesOS protocolArrhythmia scoreAcute modelDihydroethidium fluorescenceUntreated heartsVentricular tachycardiaVentricular fibrillationOxygen speciesArrhythmic consequencesElevated ROS levelsRat heartEUK-134Perfusion
2009
From mitochondrial dynamics to arrhythmias
Aon MA, Cortassa S, Akar FG, Brown DA, Zhou L, O’Rourke B. From mitochondrial dynamics to arrhythmias. The International Journal Of Biochemistry & Cell Biology 2009, 41: 1940-1948. PMID: 19703656, PMCID: PMC2732583, DOI: 10.1016/j.biocel.2009.02.016.Peer-Reviewed Original ResearchConceptsWhole cellsMitochondrial membrane potentialMode of functionMitochondrial networkOxidative stressMitochondrial dynamicsReactive oxygen speciesMitochondrial criticalityMitochondria behaveMitochondriaCellular excitabilityOxygen speciesMembrane potentialPhysiological conditionsROSCatastrophic arrhythmiasCellsCardiac cellsEnergetic failureNormal conditionsSpeciesMessengerNADHStressBroad range
2005
Mitochondrial criticality: A new concept at the turning point of life or death
Aon MA, Cortassa S, Akar FG, O'Rourke B. Mitochondrial criticality: A new concept at the turning point of life or death. Biochimica Et Biophysica Acta 2005, 1762: 232-240. PMID: 16242921, PMCID: PMC2692535, DOI: 10.1016/j.bbadis.2005.06.008.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements