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 deathMitochondriaQuantitative Assessment of Mitochondrial Morphology and Electrophysiological Function in the Diabetic Heart
Cacheux M, Rudokas M, Tieu A, Rizk J, Hummel M, Akar F. Quantitative Assessment of Mitochondrial Morphology and Electrophysiological Function in the Diabetic Heart. Methods In Molecular Biology 2024, 2803: 75-86. PMID: 38676886, DOI: 10.1007/978-1-0716-3846-0_6.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsDiabetes Mellitus, ExperimentalElectrophysiological PhenomenaMitochondria, HeartMyocardiumMyocytes, CardiacRatsConceptsMitochondrial shapeMitochondrial networkMitochondrial architectureSubcellular localizationMitochondrial morphologyDiabetic heartOxidative phosphorylationATP synthesisAction potentialsSarcolemmal ion channelsExcitation-contraction couplingFission eventsOptical action potentialsExcitation-contractionCardiac myocytesElectrophysiological properties
2016
Reducing mitochondrial bound hexokinase II mediates transition from non-injurious into injurious ischemia/reperfusion of the intact heart
Nederlof R, Gürel-Gurevin E, Eerbeek O, Xie C, Deijs GS, Konkel M, Hu J, Weber NC, Schumacher CA, Baartscheer A, Mik EG, Hollmann MW, Akar FG, Zuurbier CJ. Reducing mitochondrial bound hexokinase II mediates transition from non-injurious into injurious ischemia/reperfusion of the intact heart. Journal Of Physiology And Biochemistry 2016, 73: 323-333. PMID: 28258543, PMCID: PMC5534207, DOI: 10.1007/s13105-017-0555-3.Peer-Reviewed Original ResearchConceptsIschemia/reperfusionR injuryCardiac energeticsRecovery of functionHexokinase IISignificant LDH releasePossible underlying mechanismsIschemic insultCardiac recoveryControl heartsMtHKIIReperfusionIschemiaDHE fluorescenceRat heartR intervalLDH releasePeptide treatmentIntact heartInjuryUnderlying mechanismHeartMVO2NecrosisTreatment
2011
Disruption of Hexokinase II–Mitochondrial Binding Blocks Ischemic Preconditioning and Causes Rapid Cardiac Necrosis
Smeele KM, Southworth R, Wu R, Xie C, Nederlof R, Warley A, Nelson JK, van Horssen P, van den Wijngaard JP, Heikkinen S, Laakso M, Koeman A, Siebes M, Eerbeek O, Akar FG, Ardehali H, Hollmann MW, Zuurbier CJ. Disruption of Hexokinase II–Mitochondrial Binding Blocks Ischemic Preconditioning and Causes Rapid Cardiac Necrosis. Circulation Research 2011, 108: 1165-1169. PMID: 21527739, DOI: 10.1161/circresaha.111.244962.Peer-Reviewed Original ResearchConceptsIschemic preconditioningWild-type heartsCardiac functionProtective effectHKII levelsBaseline cardiac functionIschemia-reperfusion injuryNormal cardiac functionMitochondrial permeability transition openingContractile impairmentReperfusion injuryAcute reductionCardiac necrosisMyocardial functionGlycolytic enzymes hexokinaseCardiac contractionMild mitochondrial uncouplingMembrane depolarizationMitochondrial membrane depolarizationHKIIMitochondrial hexokinaseControl peptideHeartPreconditioningTissue disruptionMitochondria are sources of metabolic sink and arrhythmias
Akar FG, O'Rourke B. Mitochondria are sources of metabolic sink and arrhythmias. Pharmacology & Therapeutics 2011, 131: 287-294. PMID: 21513732, PMCID: PMC3138548, DOI: 10.1016/j.pharmthera.2011.04.005.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArrhythmias, CardiacCalciumHumansMitochondria, HeartMyocytes, CardiacSignal Transduction
2010
Optical imaging of mitochondrial function uncovers actively propagating waves of mitochondrial membrane potential collapse across intact heart
Lyon AR, Joudrey PJ, Jin D, Nass RD, Aon MA, O'Rourke B, Akar FG. Optical imaging of mitochondrial function uncovers actively propagating waves of mitochondrial membrane potential collapse across intact heart. Journal Of Molecular And Cellular Cardiology 2010, 49: 565-575. PMID: 20624394, PMCID: PMC3081287, DOI: 10.1016/j.yjmcc.2010.07.002.Peer-Reviewed Original ResearchAltered Spatiotemporal Dynamics of the Mitochondrial Membrane Potential in the Hypertrophied Heart
Jin H, Nass RD, Joudrey PJ, Lyon AR, Chemaly ER, Rapti K, Akar FG. Altered Spatiotemporal Dynamics of the Mitochondrial Membrane Potential in the Hypertrophied Heart. Biophysical Journal 2010, 98: 2063-2071. PMID: 20483313, PMCID: PMC2872265, DOI: 10.1016/j.bpj.2010.01.045.Peer-Reviewed Original Research
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 ResearchMeSH KeywordsAnimalsArrhythmias, CardiacHumansMembrane Potential, MitochondrialMembrane PotentialsMitochondria, HeartOxidative StressReactive Oxygen SpeciesConceptsWhole cellsMitochondrial membrane potentialMode of functionMitochondrial networkOxidative stressMitochondrial dynamicsReactive oxygen speciesMitochondrial criticalityMitochondria behaveMitochondriaCellular excitabilityOxygen speciesMembrane potentialPhysiological conditionsROSCatastrophic arrhythmiasCellsCardiac cellsEnergetic failureNormal conditionsSpeciesMessengerNADHStressBroad range
2008
Effects of 4′-chlorodiazepam on cellular excitation–contraction coupling and ischaemia–reperfusion injury in rabbit heart
Brown DA, Aon MA, Akar FG, Liu T, Sorarrain N, O’Rourke B. Effects of 4′-chlorodiazepam on cellular excitation–contraction coupling and ischaemia–reperfusion injury in rabbit heart. Cardiovascular Research 2008, 79: 141-149. PMID: 18304929, PMCID: PMC2562874, DOI: 10.1093/cvr/cvn053.Peer-Reviewed Original ResearchConceptsIschaemia-reperfusion injuryExcitation-contraction couplingReperfusion arrhythmiasRabbit heartsDose-dependent negative inotropic responseCellular excitation-contraction couplingPost-ischemic cardiac dysfunctionOnset of reperfusionMin of reperfusionSingle bolus doseNegative inotropic responseIschaemia/reperfusionIntracellular calcium transientsSarcolemmal ion channelsIsolated rabbit cardiomyocytesIon channelsCardiac action potentialContractile impairmentCardiac dysfunctionBolus doseContractile dysfunctionInotropic responseGlobal ischaemiaVoltage clamp methodCalcium current
2007
Mitochondrial Ion Channels in Cardiac Function and Dysfunction
O'Rourke B, Cortassa S, Akar F, Aon M. Mitochondrial Ion Channels in Cardiac Function and Dysfunction. Novartis Foundation Symposia 2007, 287: 140-156. PMID: 18074636, PMCID: PMC2692520, DOI: 10.1002/9780470725207.ch10.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAnimalsHeartHumansIon ChannelsMembrane Potential, MitochondrialMitochondria, HeartMyocytes, CardiacReactive Nitrogen SpeciesConceptsMitochondrial ion channelsIon channelsReactive oxygen species (ROS) signalsNumerous signaling pathwaysBurst of ROSMitochondrial networkMitochondrial physiologyPlasma membraneSpecies signalSignaling pathwaysCellular activitiesCellular targetsMitochondrial functionEnergy transductionMitochondriaVast modificationsPhysiological conditionsOrgan levelDisease developmentPotential therapeutic interventionsWidespread effectsImportant targetSurprising insightsKey roleCenter of organizations
2005
The mitochondrial origin of postischemic arrhythmias
Akar FG, Aon MA, Tomaselli GF, O'Rourke B. The mitochondrial origin of postischemic arrhythmias. Journal Of Clinical Investigation 2005, 115: 3527-3535. PMID: 16284648, PMCID: PMC1280968, DOI: 10.1172/jci25371.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsAnionsArrhythmias, CardiacDose-Response Relationship, DrugElectrophysiologyGuinea PigsHeartIntracellular MembranesIon ChannelsIschemiaMembrane PotentialsMicroscopy, ConfocalMitochondria, HeartMyocardial IschemiaMyocardial ReperfusionMyocardial Reperfusion InjuryMyocardiumMyocytes, CardiacOscillometryReactive Oxygen SpeciesReceptors, GABA-AReperfusion InjuryTemperatureTime FactorsConceptsAction potentialsVentricular fibrillationPostischemic functional recoveryIschemic heart diseaseGuinea pig heartsNew therapeutic targetsAbnormal electrical activationPostischemic arrhythmiasReperfusion arrhythmiasFunctional recoveryGlobal ischemiaHeart diseaseBolus infusionArrhythmia preventionElectrophysiological changesAP shorteningControl heartsPostischemic heartsBenzodiazepine receptorsElectrophysiological substrateTherapeutic targetArrhythmiasReperfusionPig heartsMitochondrial benzodiazepine receptor