2024
Mitofusin 2 plays a critical role in maintaining the functional integrity of the neuromuscular-skeletal axis
Zhu M, Zeiss C, Hamrick M, Weinstein R, Sun B, Brotto M, Liu X, Siu E, Huttner A, Tommasini S, Simpson C, Insogna K. Mitofusin 2 plays a critical role in maintaining the functional integrity of the neuromuscular-skeletal axis. Bone 2024, 184: 117086. PMID: 38552893, DOI: 10.1016/j.bone.2024.117086.Peer-Reviewed Original ResearchConceptsDeletion of Mfn2Bone mineral densityMitofusin 2Reduced expression of Mfn2Myofiber atrophySpinal cordTransgenic mice expressing CreMice expressing CreNon-redundant roleSkeletal muscle histologyLumbar spinal cordTrabecular bone massLean body massExpression of Mfn2Mitochondrial reticulumMFN2 geneDisruption of cellular architectureImpaired osteoblast differentiationOsteoblast lineage commitmentMfn2Mitochondrial sizeMitofusinMineral densityCo-expressionDisorganized sarcomeres
2022
Comparison of the Independent and Combined Effects of Aerobic Training and Ozone Therapy on Selected Heart Variables in Rats with Osteoarthritis
Zandi A, Matinhomaee H, Moradi L. Comparison of the Independent and Combined Effects of Aerobic Training and Ozone Therapy on Selected Heart Variables in Rats with Osteoarthritis. Pharmaceutical Chemistry Journal 2022, 56: 1033-1040. DOI: 10.1007/s11094-022-02748-2.Peer-Reviewed Original ResearchCombined effects of aerobic trainingEffects of aerobic trainingAerobic trainingOsteoarthritis interventionsAerobic exerciseRegular exerciseOzone therapyResearch variablesExerciseMfn-2 geneRisk factorsCardiovascular diseaseHeart tissueInterventionPrevent such diseasesOsteoarthritisCollagen degradationTrainingKi67 protein expressionRat heart tissueMitochondrial fission 1 proteinTissues of ratsHeart tissue of ratsMitofusin 2Ki67 proteinTargeted Deletion of Mitofusin 1 and Mitofusin 2 Causes Female Infertility and Loss of Follicular Reserve
Cozzolino M, Ergun Y, Seli E. Targeted Deletion of Mitofusin 1 and Mitofusin 2 Causes Female Infertility and Loss of Follicular Reserve. Reproductive Sciences 2022, 30: 560-568. PMID: 35739352, DOI: 10.1007/s43032-022-01014-w.Peer-Reviewed Original ResearchConceptsMitofusin 1Mitofusin 2Double deletionFemale reproductive competencePotential functional redundancyDynamic organellesCellular homeostasisFunctional redundancyMitochondrial dynamicsEnvironmental stressMitochondrial functionMitochondrial dysfunctionMfn1Reproductive competenceTargeted deletionMfn2Oocyte maturationDeletionCritical roleReproductive agingFemale infertilityOocytesOocyte qualityFusion mechanismMitofusins
2021
Mitofusin-2 regulates leukocyte adhesion and β2 integrin activation
Liu W, Hsu AY, Wang Y, Lin T, Sun H, Pachter JS, Groisman A, Imperioli M, Yungher FW, Hu L, Wang P, Deng Q, Fan Z. Mitofusin-2 regulates leukocyte adhesion and β2 integrin activation. Journal Of Leukocyte Biology 2021, 111: 771-791. PMID: 34494308, PMCID: PMC8901796, DOI: 10.1002/jlb.1a0720-471r.Peer-Reviewed Original ResearchConceptsΒ2 integrin activationIntegrin activationMitofusin 2Mfn2 deficiencyConformation-specific monoclonal antibodiesMFN2 knockdownHL60 cellsNeutrophil-like HL60 cellsMolecular detailsActin polymerizationCell spreadingAdhesion defectsReduced expressionInnate immunityKnockdownNew insightsActivationCellsLeukocyte adhesionAdhesionCell rollingCrucial stepMonoclonal antibodiesDifferentiationVascular endotheliumAbnormal levels of mitochondrial proteins in plasma neuronal extracellular vesicles in major depressive disorder
Goetzl EJ, Wolkowitz OM, Srihari VH, Reus VI, Goetzl L, Kapogiannis D, Heninger GR, Mellon SH. Abnormal levels of mitochondrial proteins in plasma neuronal extracellular vesicles in major depressive disorder. Molecular Psychiatry 2021, 26: 7355-7362. PMID: 34471251, PMCID: PMC8872999, DOI: 10.1038/s41380-021-01268-x.Peer-Reviewed Original ResearchConceptsNeuron-derived extracellular vesiclesMitochondrial proteinsCyclophilin DMitofusin 2Extracellular vesiclesFunctional mitochondrial proteinsElectron transport complexes INuclear respiratory factorOpen-reading frameNeuronal extracellular vesiclesNew drug targetsΓ coactivator 1αPenultimate enzymeTranscription factorsMajor depressive disorderLeucine zipperMyosin VIGene responsesMitochondrial biogenesisPotential biomarker proteinsProtein componentsSelective serotonin reuptake inhibitorsPPAR-γ coactivator 1αComplex IDrug targetsMitofusin‐2 regulates leukocyte adhesion through the maturation of β2 integrin activation in differentiation
Fan Z, Liu W, Wang Y, Hsu A, Lin T, Sun H, Pachter J, Groisman A, Imperioli M, Yungher F, Hu L, Wang P, Deng Q. Mitofusin‐2 regulates leukocyte adhesion through the maturation of β2 integrin activation in differentiation. The FASEB Journal 2021, 35 DOI: 10.1096/fasebj.2021.35.s1.00211.Peer-Reviewed Original ResearchΒ2 integrin activationNeutrophil adhesionLeukocyte adhesionMitofusin 2HL60 cellsIntegrin activationNeutrophil recruitmentNeutrophil-like HL60 cellsVascular endotheliumFMLP receptorInnate immunityReduced expressionΒ2 integrinsConformational specific antibodiesMitofusin 2 deficiencyActivationCellsMaturationCD35InflammationNeutrophilsEndotheliumDiseaseΒ2ImmunityNeural cell‐derived plasma exosome protein abnormalities implicate mitochondrial impairment in first episodes of psychosis
Goetzl EJ, Srihari VH, Guloksuz S, Ferrara M, Tek C, Heninger GR. Neural cell‐derived plasma exosome protein abnormalities implicate mitochondrial impairment in first episodes of psychosis. The FASEB Journal 2021, 35: e21339. PMID: 33454965, DOI: 10.1096/fj.202002519r.Peer-Reviewed Original ResearchMeSH KeywordsAdultAstrocytesDNA-Binding ProteinsExosomesFemaleGTP PhosphohydrolasesHumansIntracellular Signaling Peptides and ProteinsMaleMitochondriaMitochondrial ProteinsMitochondrial Proton-Translocating ATPasesMyosin Heavy ChainsNeuronsPeptidyl-Prolyl Isomerase FPsychotic DisordersTranscription FactorsConceptsNeuron-derived extracellular vesiclesFunctional proteinsMitochondrial functional proteinsMitochondrial protein mitofusin 2Extracellular vesiclesMitochondrial ATP synthaseMitochondrial ATP synthase activityATP synthase activityTranscription factor AMitochondrial proteinsATP synthaseMyosin VICyclophilin DConversion of NADHMitofusin 2EV contentExosome markersPeptide humaninProteinMitochondrial impairmentSynthase activityProtein levelsFactor AMitochondriaVesicles
2019
Mitofusin 2 plays a role in oocyte and follicle development, and is required to maintain ovarian follicular reserve during reproductive aging
Zhang M, Bener MB, Jiang Z, Wang T, Esencan E, Scott R, Horvath T, Seli E. Mitofusin 2 plays a role in oocyte and follicle development, and is required to maintain ovarian follicular reserve during reproductive aging. Aging 2019, 11: 3919-3938. PMID: 31204316, PMCID: PMC6628992, DOI: 10.18632/aging.102024.Peer-Reviewed Original ResearchConceptsMitofusin 2Key regulatory proteinsImpaired oocyte maturationFollicle developmentMitochondrial fusionRegulatory proteinsEndoplasmic reticulumMitochondrial dysfunctionTargeted deletionOocyte maturationOocytesReproductive agingFemale subfertilityOocyte qualityOvarian follicular reserveTelomeresMitochondriaMetabolic milieuProteinReticulumDeletionFusionPhenotypeApoptosisMaturationPolycystin 2 regulates mitochondrial Ca2+ signaling, bioenergetics, and dynamics through mitofusin 2
Kuo IY, Brill AL, Lemos FO, Jiang JY, Falcone JL, Kimmerling EP, Cai Y, Dong K, Kaplan DL, Wallace DP, Hofer AM, Ehrlich BE. Polycystin 2 regulates mitochondrial Ca2+ signaling, bioenergetics, and dynamics through mitofusin 2. Science Signaling 2019, 12 PMID: 31064883, PMCID: PMC6855602, DOI: 10.1126/scisignal.aat7397.Peer-Reviewed Original ResearchConceptsEndoplasmic reticulumPC2 knockdownMitochondrial CaCell culture modelKnockdown of Mfn2Polycystin-2 functionsHuman ADPKD kidneysAutosomal dominant polycystic kidney diseaseKey mitochondrial proteinsAberrant cell proliferationMitochondria-ER contactsCell proliferationER-mitochondrial interfaceKidney cystsIntimate functional relationshipNumerous fluid-filled cystsMitochondrial proteinsCyst-lining epithelial cellsMitofusin 2 expressionCulture modelPolycystin-2Knockdown cellsMitochondrial biogenesisMitofusin 2Mitochondrial respirationMitofusin 2 in Mature Adipocytes Controls Adiposity and Body Weight
Mancini G, Pirruccio K, Yang X, Blücher M, Rodeheffer M, Horvath TL. Mitofusin 2 in Mature Adipocytes Controls Adiposity and Body Weight. Cell Reports 2019, 26: 2849-2858.e4. PMID: 30865877, PMCID: PMC6876693, DOI: 10.1016/j.celrep.2019.02.039.Peer-Reviewed Original ResearchConceptsKnockout miceBody weightMitochondria-endoplasmic reticulum interactionSystemic metabolic dysregulationImpaired glucose metabolismHigh-fat dietObese human subjectsCalorie-dense foodsMitofusin 2Control miceStandard chowLean controlsMetabolic dysregulationFood intakeAdult miceGlucose metabolismStandard dietAdipose tissueBrown fatGlucose utilizationAdiposityTissue levelsSystemic levelsMiceAdult animals
2013
Mitochondrial Dynamics Controlled by Mitofusins Regulate Agrp Neuronal Activity and Diet-Induced Obesity
Dietrich MO, Liu ZW, Horvath TL. Mitochondrial Dynamics Controlled by Mitofusins Regulate Agrp Neuronal Activity and Diet-Induced Obesity. Cell 2013, 155: 188-199. PMID: 24074868, PMCID: PMC4142434, DOI: 10.1016/j.cell.2013.09.004.Peer-Reviewed Original ResearchConceptsMitochondrial dynamicsEnergy metabolismCell-type specificCellular energy metabolismWhole-body energy metabolismKey organellesMitofusin 1Mitofusin 2High-fat dietMitochondria sizeAgRP neuronsMfn1Anorexigenic pro-opiomelanocortin (POMC) neuronsAgRP neuronal activityKnockout miceMetabolismPro-opiomelanocortin (POMC) neuronsFusion mechanismDiet-induced obesityMitofusinsOverfed stateImportant roleCellsDynamic changesOrganellesMitofusin 2 in POMC Neurons Connects ER Stress with Leptin Resistance and Energy Imbalance
Schneeberger M, Dietrich MO, Sebastián D, Imbernón M, Castaño C, Garcia A, Esteban Y, Gonzalez-Franquesa A, Rodríguez IC, Bortolozzi A, Garcia-Roves PM, Gomis R, Nogueiras R, Horvath TL, Zorzano A, Claret M. Mitofusin 2 in POMC Neurons Connects ER Stress with Leptin Resistance and Energy Imbalance. Cell 2013, 155: 172-187. PMID: 24074867, PMCID: PMC3839088, DOI: 10.1016/j.cell.2013.09.003.Peer-Reviewed Original ResearchConceptsHypothalamic ER stressER stress-induced leptin resistanceLeptin resistanceMitofusin 2ER stressMitochondria-endoplasmic reticulum interactionAnorexigenic pro-opiomelanocortin (POMC) neuronsPro-opiomelanocortin (POMC) neuronsDiet-induced obesityMitochondria-ER contactsSystemic energy balancePOMC neuronsMetabolic alterationsCausative factorsEnergy expenditurePOMC processingObesityUnderlying mechanismCrucial involvementNeuronsEnergy imbalanceEssential regulatorCritical roleHyperphagiaHypothalamus
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