2025
1824-P: Bioenergetic Advantage of Pyruvate Kinase Overcomes Mitochondrial OXPHOS in Beta-Cells to Initiate Insulin Secretion
RUZ-MALDONADO I, CARDONE R, MERRINS M, KIBBEY R. 1824-P: Bioenergetic Advantage of Pyruvate Kinase Overcomes Mitochondrial OXPHOS in Beta-Cells to Initiate Insulin Secretion. Diabetes 2025, 74 DOI: 10.2337/db25-1824-p.Peer-Reviewed Original ResearchPyruvate kinaseATP/ADP ratioMitochondrial OXPHOSHuman isletsBeta-cellsIntact miceOxygen consumption rateKATP channel closureInsulin secretionMitochondrial membrane potentialPlasma membrane depolarizationDose-dependent mannerIntramitochondrial ADPADP availabilityHyperpolarized mitochondriaInitial insulin secretionKATP channelsMitochondrial hyperpolarizationOXPHOS inhibitionINS-1Pyruvate metabolismETC complexesMembrane depolarizationATP synthesisOXPHOS1840-P: Pyruvate Kinase Bioenergetically Restricts OXPHOS in Beta Cells and Myotubules by Inducing Mitochondrial Membrane Hyperpolarization
DAVIDSON E, KIBBEY R. 1840-P: Pyruvate Kinase Bioenergetically Restricts OXPHOS in Beta Cells and Myotubules by Inducing Mitochondrial Membrane Hyperpolarization. Diabetes 2025, 74 DOI: 10.2337/db25-1840-p.Peer-Reviewed Original ResearchMitochondrial membrane potentialPyruvate kinaseHyperpolarization of mitochondrial membrane potentialRespiratory suppressionMitochondrial membrane potential differenceMitochondrial membrane hyperpolarizationCytosolic ATP/ADP ratioComplex V activityDigestive and Kidney DiseasesINS-1ATP hydrolysisATP synthesisPhosphoenolpyruvateMembrane hyperpolarizationPK substratesBlocking electron transportOXPHOSKidney diseaseATP/ADP ratioBeta cellsHyperpolarizationMembrane potentialPK activityState 3OligosP-623 MFF is required for mitochondria-associated ribonucleoprotein domain coalescence and mRNA translation in mammalian oocytes
Hua R, Zhuo H, Gu J, Du H, Xiao Y, Yeung W, Wang T. P-623 MFF is required for mitochondria-associated ribonucleoprotein domain coalescence and mRNA translation in mammalian oocytes. Human Reproduction 2025, 40: deaf097.929. DOI: 10.1093/humrep/deaf097.929.Peer-Reviewed Original ResearchMitochondrial fission factorMitochondrial membrane potentialRNA-binding proteinsMammalian oocytesMouse oocytesMRNA translational activityMRNA translationGerminal vesicle (GV)-stage oocytesCo-IPMitochondrial dynamicsOocyte meiotic maturationRegulation of mitochondrial dynamicsMetaphase I stageTranslational activityGV stageGV oocytesRegulation of translationJC-1 stainingATP metabolic processRegulate mRNA translationWestern blot analysisGene ontology analysisMeiotic maturationWider implicationsOocyte maturationP-551. The Effects of Antiretroviral Therapy on Immune Activation, Inflammation, Cellular Changes and Clinical Outcomes in Elite Controllers
Chan E, Zhou L, Emu B, Paintsil E, Barakat L. P-551. The Effects of Antiretroviral Therapy on Immune Activation, Inflammation, Cellular Changes and Clinical Outcomes in Elite Controllers. Open Forum Infectious Diseases 2025, 12: ofae631.750. PMCID: PMC11777457, DOI: 10.1093/ofid/ofae631.750.Peer-Reviewed Original ResearchEffects of antiretroviral therapyAntiretroviral therapyElite controllersViral loadIL-6Inflammatory markersImmune activationReactive oxygen speciesReactive oxygen species productionAdverse effects of ARTMitochondrial membrane potentialBenefits of antiretroviral therapyAntiretroviral Therapy ToxicitiesInflammatory markers IL-6Antiretroviral therapy groupHIV viral loadMembrane potentialCurrent published dataUtilization of antiretroviral therapyCellular inflammatory markersCompared to baselineViremic controllersClinical outcomesCRP decreaseLevels of mtDNA deletions
2023
Mitochondria-targeted cyclometalated iridium-β-carboline complexes as potent non-small cell lung cancer therapeutic agents
Chen J, Guo X, Li D, Tang H, Gao J, Yu W, Zhu X, Sun Z, Huang Z, Chen L. Mitochondria-targeted cyclometalated iridium-β-carboline complexes as potent non-small cell lung cancer therapeutic agents. Metallomics 2023, 15: mfad035. PMID: 37204038, DOI: 10.1093/mtomcs/mfad035.Peer-Reviewed Original ResearchConceptsLoss of mitochondrial membrane potentialIridium complexesDeath of A549 cellsMitochondrial membrane potentialA549 cellsDepletion of cellular ATPElevation of reactive oxygen speciesNSCLC therapeutic agentsMitochondrial eventsCaspase pathwayCancer therapeutic agentsReactive oxygen speciesPotential antitumor effectsCellular ATPDevelopment of antitumor drugsMulticellular tumor spheroid modelAntitumor effectNon-smallTumor spheroid modelTumor growthMembrane potentialIridiumOxygen speciesTherapeutic agentsAntitumor drugsMitochondrial stress response gene Clpp deficiency impairs oocyte competence and deteriorate cyclophosphamide-induced ovarian damage in young mice
Li G, Gu J, Zhou X, Wu T, Li X, Hua R, Hai Z, Xiao Y, Su J, Yeung W, Liu K, Guo C, Wang T. Mitochondrial stress response gene Clpp deficiency impairs oocyte competence and deteriorate cyclophosphamide-induced ovarian damage in young mice. Frontiers In Endocrinology 2023, 14: 1122012. PMID: 37033217, PMCID: PMC10081448, DOI: 10.3389/fendo.2023.1122012.Peer-Reviewed Original ResearchConceptsCyclophosphamide-induced ovarian damageOvarian damageOocyte-specific deletionOocyte competencePremature ovarian insufficiencyImpaired oocyte competenceChemotherapeutic drug cyclophosphamideCaseinolytic peptidase PDecreased mitochondrial membrane potentialAneuploidy rateMII oocytesCTX treatmentElevated ROS levelsOvarian insufficiencyEarly folliculogenesisKnockout miceYoung miceMitochondrial membrane potentialMouse modelDrug cyclophosphamideTreat cancerMiceOocytesSpindle rateMembrane potential
2022
Development of an Open Microfluidic Platform for Oocyte One-Stop Vitrification with Cryotop Method
Miao S, Guo C, Jiang Z, Wei H, Jiang X, Gu J, Hai Z, Wang T, Liu Y. Development of an Open Microfluidic Platform for Oocyte One-Stop Vitrification with Cryotop Method. Biosensors 2022, 12: 766. PMID: 36140151, PMCID: PMC9496857, DOI: 10.3390/bios12090766.Peer-Reviewed Original ResearchConceptsCryotop methodMitochondrial membrane potentialMicrofluidic systemReactive oxygen speciesLevels of oocytesEffect of vitrificationCryoprotective agentsOocyte vitrificationRisk of cell lossOpen microfluidic systemTreated oocytesFertility preservationCell transferCryotopReproductive centerCell lossSurvival rateOpen microfluidic chipOocytesAssisted reproductionSufficient cooling rateMembrane potentialProcessing chipOpen microfluidic platformAutomatic microfluidic systemPET imaging of mitochondrial function in acute doxorubicin-induced cardiotoxicity: a proof-of-principle study
Detmer F, Alpert N, Moon S, Dhaynaut M, Guerrero J, Guehl N, Xing F, Brugarolas P, Shoup T, Normandin M, Pelletier-Galarneau M, El Fakhri G, Petibon Y. PET imaging of mitochondrial function in acute doxorubicin-induced cardiotoxicity: a proof-of-principle study. Scientific Reports 2022, 12: 6122. PMID: 35414642, PMCID: PMC9005533, DOI: 10.1038/s41598-022-10004-6.Peer-Reviewed Original ResearchConceptsLeft anterior descending coronary arteryDoxorubicin-induced cardiotoxicityCardiac membrane potentialDoxorubicin infusionMembrane potentialAnimal modelsAcute doxorubicin-induced cardiotoxicityLeft anterior descending coronary artery territoryAcute cardiotoxic effectsAnterior descending coronary arteryControl saline infusionDescending coronary arteryDoxorubicin doseSaline infusionTest infusionCardiotoxic effectsMitochondrial membrane potentialInfusion catheterCoronary arteryInfusionMitochondrial functionDoxorubicinMyocardial areaPET imagingIntracoronary catheter
2021
Quantification of Myocardial Mitochondrial Membrane Potential Using PET
Pelletier-Galarneau M, Detmer F, Petibon Y, Normandin M, Ma C, Alpert N, El Fakhri G. Quantification of Myocardial Mitochondrial Membrane Potential Using PET. Current Cardiology Reports 2021, 23: 70. PMID: 33970353, PMCID: PMC8443083, DOI: 10.1007/s11886-021-01500-8.Peer-Reviewed Original ResearchATPIF1 maintains normal mitochondrial structure which is impaired by CCM3 deficiency in endothelial cells
Wang K, Chen H, Zhou Z, Zhang H, Zhou HJ, Min W. ATPIF1 maintains normal mitochondrial structure which is impaired by CCM3 deficiency in endothelial cells. Cell & Bioscience 2021, 11: 11. PMID: 33422124, PMCID: PMC7796565, DOI: 10.1186/s13578-020-00514-z.Peer-Reviewed Original ResearchActivation of mitophagyHuman umbilical vein endothelial cellsNormal mitochondrial structureMorphology of mitochondriaRNA-seq screeningMitochondrial membrane potentialCRISPR-Cas9 SystemCerebral cavernous malformationsEndothelial cellsExpression of KLF4Destruction of mitochondriaUmbilical vein endothelial cellsMitochondrial structureSignaling pathwaysVein endothelial cellsMitochondriaATPIF1MitophagyEndothelial progenitor cellsProgenitor cellsCell proliferationMembrane potentialKLF4PathwayProtein
2020
In vivo quantitative mapping of human mitochondrial cardiac membrane potential: a feasibility study
Pelletier-Galarneau M, Petibon Y, Ma C, Han P, Kim S, Detmer F, Yokell D, Guehl N, Normandin M, El Fakhri G, Alpert N. In vivo quantitative mapping of human mitochondrial cardiac membrane potential: a feasibility study. European Journal Of Nuclear Medicine And Molecular Imaging 2020, 48: 414-420. PMID: 32719915, PMCID: PMC7839097, DOI: 10.1007/s00259-020-04878-9.Peer-Reviewed Original ResearchConceptsMembrane potentialBolus injectionHealthy subjectsHematocrit levelsSerial venous blood samplesT1 mapping imagesVenous blood samplesExtracellular space fractionMethodsThirteen healthy subjectsDynamic PET acquisitionCellular membrane potentialGadolinium injectionPrognostic informationVentricular arrhythmiasHeart failureMyocardial hypertrophyMitochondrial membrane potentialCardiac diseaseIn vitro assessmentTherapy monitoringBlood concentrationsPET acquisitionImaging protocolBlood samplesPlasma tracer concentrationIn-vivo Imaging of Mitochondrial Depolarization of Myocardium With Positron Emission Tomography and a Proton Gradient Uncoupler
Alpert N, Pelletier-Galarneau M, Kim S, Petibon Y, Sun T, Ramos-Torres K, Normandin M, Fakhri G. In-vivo Imaging of Mitochondrial Depolarization of Myocardium With Positron Emission Tomography and a Proton Gradient Uncoupler. Frontiers In Physiology 2020, 11: 491. PMID: 32499721, PMCID: PMC7243673, DOI: 10.3389/fphys.2020.00491.Peer-Reviewed Original ResearchMitochondrial membrane potentialPositron emission tomographyProton gradient uncouplerMembrane potentialIntracoronary infusionEmission tomographyPositron emission tomography scanBolus plus infusionVolume of distributionMitochondrial membraneCellular membrane potentialBAM15InfusionPreliminary dose-response experimentsMaximum depolarizationDose-response experimentsIn vivo imagingSecular equilibriumCytoprotective effects of (E)-N-(2-(3, 5-dimethoxystyryl) phenyl) furan-2-carboxamide (BK3C231) against 4-nitroquinoline 1-oxide-induced damage in CCD-18Co human colon fibroblast cells
Tan H, Thomas N, Inayat-Hussain S, Chan K. Cytoprotective effects of (E)-N-(2-(3, 5-dimethoxystyryl) phenyl) furan-2-carboxamide (BK3C231) against 4-nitroquinoline 1-oxide-induced damage in CCD-18Co human colon fibroblast cells. PLOS ONE 2020, 15: e0223344. PMID: 32365104, PMCID: PMC7197815, DOI: 10.1371/journal.pone.0223344.Peer-Reviewed Original ResearchConceptsNormal human colon fibroblastMitochondrial damageMitochondrial membrane potentialNitrosative stressHuman colon fibroblastsN-furanDNA strand breaksCellular DNACCD-18Co cellsCytoprotective effectsStrand breaksColon fibroblastsProtein expressionDNAMembrane potentialFibroblast cellsMicronucleus formationOxidative stressCytoprotective potentialCell modelGroup of chemicalsCellsNitric oxide levelsPotential chemopreventive activityGlutathione levels
2019
Alpha-Tocotrienol Prevents Oxidative Stress-Mediated Post-Translational Cleavage of Bcl-xL in Primary Hippocampal Neurons
Park HA, Mnatsakanyan N, Broman K, Davis AU, May J, Licznerski P, Crowe-White KM, Lackey KH, Jonas EA. Alpha-Tocotrienol Prevents Oxidative Stress-Mediated Post-Translational Cleavage of Bcl-xL in Primary Hippocampal Neurons. International Journal Of Molecular Sciences 2019, 21: 220. PMID: 31905614, PMCID: PMC6982044, DOI: 10.3390/ijms21010220.Peer-Reviewed Original ResearchConceptsPrimary hippocampal neuronsHippocampal neuronsReactive oxygen speciesMitochondrial dysfunctionBcl-xLMitochondrial membrane potentialMitochondrial functionProduction of ROSExcitotoxic conditionsGlutamate challengeNeuroprotective propertiesMembrane potentialNeuronal deathExcitotoxic stimulationBcl-xL levelsNeuronal survivalIntracellular ATP depletionMitochondrial reactive oxygen speciesB cellsImportant causeDysfunctionNeuronsROS productionATP depletionNeurite outgrowth463P Evaluation of pharmacodynamic (PD) biomarkers in advanced cancer patients treated with oxidative phosphorylation (OXPHOS) inhibitor, OPC-317 (OPC)
Eu J, Yadav K, Lim Y, Hirpara J, Kong L, Ng Z, Lee V, Lee S, Tan D, Soo R, Chee C, Yong W, Sundar R, Lim J, Wang L, Ohi N, Tsunoda T, Pervaiz S, Goh B, Wong A. 463P Evaluation of pharmacodynamic (PD) biomarkers in advanced cancer patients treated with oxidative phosphorylation (OXPHOS) inhibitor, OPC-317 (OPC). Annals Of Oncology 2019, 30: v174. DOI: 10.1093/annonc/mdz244.025.Peer-Reviewed Original ResearchMitochondrial membrane potentialSerum metabolomeHER2+ breast cancerOncogene-addicted tumorsDose-finding phaseClinically tolerable dosesCancer stem cellsNon-significant riseG3/4 toxicitiesOxidative phosphorylation inhibitionSignificantly with treatmentGIST patientsTolerated doseTumor biopsiesImmunohistochemistry expressionCopy numberOxidative phosphorylationSerum lactateBreast cancerClinical developmentDrug resistanceMerck SeronoDose levelsDay 1Pathway inhibitor
2018
Quantitative in vivo mapping of myocardial mitochondrial membrane potential
Alpert N, Guehl N, Ptaszek L, Pelletier-Galarneau M, Ruskin J, Mansour M, Wooten D, Ma C, Takahashi K, Zhou Y, Shoup T, Normandin M, Fakhri G. Quantitative in vivo mapping of myocardial mitochondrial membrane potential. PLOS ONE 2018, 13: e0190968. PMID: 29338024, PMCID: PMC5770041, DOI: 10.1371/journal.pone.0190968.Peer-Reviewed Original Research
2017
Mitochondrial ROS activates ERK/autophagy pathway as a protected mechanism against deoxypodophyllotoxin-induced apoptosis
Kim SH, Kim KY, Park SG, Yu SN, Kim YW, Nam HW, An HH, Kim YW, Ahn SC. Mitochondrial ROS activates ERK/autophagy pathway as a protected mechanism against deoxypodophyllotoxin-induced apoptosis. Oncotarget 2017, 5: 111581-111596. PMID: 29340076, PMCID: PMC5762344, DOI: 10.18632/oncotarget.22875.Peer-Reviewed Original ResearchMitochondrial reactive oxygen speciesReactive oxygen speciesCell death responseMultiple cellular processesProtein 1 light chain 3Apoptotic prostate cancer cellsSelective fluorescent dyeMicrotubule-associated protein 1 light chain 3Acidic vesicular organellesMitochondrial membrane potentialG2/M cell cycle arrestM cell cycle arrestCell cycle arrestLight chain 3LC3 knockdownCellular processesDeath responseInhibition of autophagyApoptosis-related proteinsVesicular organellesAutophagy pathwayMolecular mechanismsCellular responsesProstate cancer cell linesProstate cancer cellsInhibition of Bcl-xL prevents pro-death actions of ΔN-Bcl-xL at the mitochondrial inner membrane during glutamate excitotoxicity
Park HA, Licznerski P, Mnatsakanyan N, Niu Y, Sacchetti S, Wu J, Polster BM, Alavian KN, Jonas EA. Inhibition of Bcl-xL prevents pro-death actions of ΔN-Bcl-xL at the mitochondrial inner membrane during glutamate excitotoxicity. Cell Death & Differentiation 2017, 24: 1963-1974. PMID: 28777375, PMCID: PMC5635221, DOI: 10.1038/cdd.2017.123.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsbcl-X ProteinBiphenyl CompoundsCell DeathCyclosporineGlutamic AcidMembrane Potential, MitochondrialMitochondrial MembranesMitochondrial Proton-Translocating ATPasesModels, BiologicalMutant ProteinsNeuritesNeurotoxinsNitrophenolsPiperazinesProtein SubunitsRats, Sprague-DawleyRhodaminesSulfonamidesConceptsBcl-xLABT-737ΔN-BclMitochondrial membraneWEHI-539ATP synthase c-subunitMitochondrial inner membrane depolarizationPro-death actionInner membrane depolarizationMitochondrial inner membraneOuter mitochondrial membraneMitochondrial inner membrane potentialATP synthase activityActivation of BaxInner membrane potentialMitochondrial permeability transition poreMitochondrial membrane potentialMembrane potentialPermeability transition poreAnti-apoptotic activityC subunitInner membraneB-cell lymphoma extra-large proteinBax activationGlutamate toxicityInhibition of Autophagy Promotes Salinomycin-Induced Apoptosis via Reactive Oxygen Species-Mediated PI3K/AKT/mTOR and ERK/p38 MAPK-Dependent Signaling in Human Prostate Cancer Cells
Kim K, Park K, Kim S, Yu S, Park S, Kim Y, Seo Y, Ma J, Ahn S. Inhibition of Autophagy Promotes Salinomycin-Induced Apoptosis via Reactive Oxygen Species-Mediated PI3K/AKT/mTOR and ERK/p38 MAPK-Dependent Signaling in Human Prostate Cancer Cells. International Journal Of Molecular Sciences 2017, 18: 1088. PMID: 28524116, PMCID: PMC5454997, DOI: 10.3390/ijms18051088.Peer-Reviewed Original ResearchMeSH KeywordsApoptosisAutophagyCell ProliferationExtracellular Signal-Regulated MAP KinasesFlavonoidsHumansImidazolesMaleMAP Kinase Signaling SystemMembrane Potential, Mitochondrialp38 Mitogen-Activated Protein KinasesPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsProto-Oncogene Proteins c-aktPyransPyridinesReactive Oxygen SpeciesTOR Serine-Threonine KinasesConceptsExtracellular signal-regulated kinasePI3K/Akt/mTORProstate cancer cellsAkt/mTORCancer cellsP38 MAPK-dependent signalingUpregulation of ERKSignal-regulated kinaseMAPK-dependent signalingP38 MAPK signaling pathwaysMitochondrial membrane potentialMAPK signaling pathwaysChemo-resistant cancersHuman prostate cancer cellsReactive oxygen species productionInhibition of autophagyPI3K inhibitorsPotential antitumor mechanismAcridine orange stainingCaspase-3 activityOxygen species productionSignaling pathwaysP38 inhibitorPropidium iodide assayMTOR activitySalinomycin Induces Reactive Oxygen Species and Apoptosis in Aggressive Breast Cancer Cells as Mediated with Regulation of Autophagy
Kim K, Park K, Kim S, Yu S, Lee D, Kim Y, Noh K, YEUL J, Seo Y, Ahn S. Salinomycin Induces Reactive Oxygen Species and Apoptosis in Aggressive Breast Cancer Cells as Mediated with Regulation of Autophagy. Anticancer Research 2017, 37: 1747-1758. PMID: 28373437, DOI: 10.21873/anticanres.11507.Peer-Reviewed Original ResearchConceptsMDA-MB-231 cellsAggressive breast cancer cellsBreast cancer cellsCancer cellsReactive oxygen speciesBreast cancer cell linesROS productionMitochondrial membrane potentialScavenger of ROSInduces reactive oxygen speciesCancer cell linesCaspase-3/9 activityPropidium iodide stainingMCF-7 cellsOxygen speciesAcceleration of apoptosisAcridine orange stainingAutophagy inhibitionMonocarboxylic ionophoreChemotherapeutic drugsCancer treatmentMitochondrial dysfunctionIodide stainingRegulation of autophagyUnderlying mechanism
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