2024
Disruption of mitochondrial unfolded protein response results in telomere shortening in mouse oocytes and somatic cells
Cozzolino M, Ergun Y, Ristori E, Garg A, Imamoglu G, Seli E. Disruption of mitochondrial unfolded protein response results in telomere shortening in mouse oocytes and somatic cells. Aging 2024, 16: 2047-2060. PMID: 38349865, PMCID: PMC10911389, DOI: 10.18632/aging.205543.Peer-Reviewed Original ResearchMeSH KeywordsAgingAnimalsFemaleHumansInfertility, FemaleMiceOocytesTelomeraseTelomereTelomere ShorteningUnfolded Protein ResponseConceptsCaseinolytic peptidase PMitochondrial unfolded protein responseUnfolded protein responseTelomere integrityProtein responseGermline deletionSomatic cellsSomatic agingSomatic cell divisionDouble-stranded DNA breaksAged miceTelomere shorteningAssociated with cellular senescenceTelomeric regionsProtein homeostasisAccelerated follicular depletionChromosome stabilityCell divisionMtUPRDNA breaksTelomereAging phenotypesCellular senescenceFollicular depletionMouse oocytesMitochondrial Unfolded Protein Response Gene Clpp Is Required for Oocyte Function and Female Fertility
Ergun Y, Imamoglu A, Cozzolino M, Demirkiran C, Basar M, Garg A, Yildirim R, Seli E. Mitochondrial Unfolded Protein Response Gene Clpp Is Required for Oocyte Function and Female Fertility. International Journal Of Molecular Sciences 2024, 25: 1866. PMID: 38339144, PMCID: PMC10855406, DOI: 10.3390/ijms25031866.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsEndopeptidase ClpFemaleFertilityInfertility, FemaleMiceMitochondriaOocytesUnfolded Protein ResponseConceptsCaseinolytic peptidase PMouse modelProtein homeostasisStress responseUnfolded protein stress responseProtein stress responseCumulus/granulosa cellsOocyte competenceOocyte functionGlobal deletionFunctional abnormalitiesGenes clpPMetabolic stress responseFemale subfertilityFemale infertilityOocyte-specificOocytesReproductive functionMtUPRMiceProtein degradationReproductive competenceFemale fertilityDeletionHomeostasis
2020
Mitochondrial function in women with polycystic ovary syndrome.
Cozzolino M, Seli E. Mitochondrial function in women with polycystic ovary syndrome. Current Opinion In Obstetrics & Gynecology 2020, 32: 205-212. PMID: 32068544, DOI: 10.1097/gco.0000000000000619.Peer-Reviewed Original ResearchConceptsPolycystic ovary syndromeLower mtDNA copy numberOvary syndromePathogenesis of PCOSMitochondrial dysfunctionMtDNA copy numberPotential protective rolePCOS phenotypeInsulin resistancePathophysiological mechanismsCommon findingDiagnostic modalitiesMetabolic milieuFunctional alterationsMitochondrial functional alterationsProtective roleCommon diseaseOxidative stressWomenMitochondrial functionDysfunctionSyndromeCopy numberProtein responseReactive oxygenImpaired Mitochondrial Stress Response due to CLPP Deletion Is Associated with Altered Mitochondrial Dynamics and Increased Apoptosis in Cumulus Cells
Esencan E, Jiang Z, Wang T, Zhang M, Soylemez-Imamoglu G, Seli E. Impaired Mitochondrial Stress Response due to CLPP Deletion Is Associated with Altered Mitochondrial Dynamics and Increased Apoptosis in Cumulus Cells. Reproductive Sciences 2020, 27: 621-630. PMID: 31939198, DOI: 10.1007/s43032-019-00063-y.Peer-Reviewed Original ResearchConceptsCaseinolytic peptidase PCumulus cell functionClpP deletionMitochondrial unfolded protein responseMitochondrial stress responseCumulus cellsUnfolded protein responseRNA sequencing analysisAltered mitochondrial dynamicsCell functionProtein homeostasisMitochondrial dynamics genesCLPP resultsMitochondrial dynamicsDynamic genesPhagosome pathwayProtein responseCellular metabolismGene expressionWild typeStress responseCumulus oophorus complexesMitochondrial ultrastructureSequencing analysisApoptotic activity
2019
Mitochondrial unfolded protein response: a stress response with implications for fertility and reproductive aging
Seli E, Wang T, Horvath TL. Mitochondrial unfolded protein response: a stress response with implications for fertility and reproductive aging. Fertility And Sterility 2019, 111: 197-204. PMID: 30691623, DOI: 10.1016/j.fertnstert.2018.11.048.Peer-Reviewed Original ResearchConceptsMitochondrial unfolded protein responseTwo-cell embryo developmentUnfolded protein responseImpaired oocyte maturationMorphology of mitochondriaMitochondrial dysfunction resultsPremature reproductive agingNovel mechanistic insightsMitochondrial DNA contentReactive oxygen species productionPrevention of agingCLPP resultsProtein responseOxygen species productionReproductive agingPreimplantation embryosAge-related accumulationOxidative phosphorylationStress responseEmbryo developmentForm blastocystsMitochondrial functionMitochondriaMitochondrial dysfunctionEnergy metabolism
2018
Mitochondrial unfolded protein response gene Clpp is required to maintain ovarian follicular reserve during aging, for oocyte competence, and development of pre‐implantation embryos
Wang T, Babayev E, Jiang Z, Li G, Zhang M, Esencan E, Horvath T, Seli E. Mitochondrial unfolded protein response gene Clpp is required to maintain ovarian follicular reserve during aging, for oocyte competence, and development of pre‐implantation embryos. Aging Cell 2018, 17: e12784. PMID: 29851234, PMCID: PMC6052477, DOI: 10.1111/acel.12784.Peer-Reviewed Original ResearchMeSH KeywordsAgingAnimalsEmbryonic DevelopmentEndopeptidase ClpFemaleMiceMice, KnockoutMitochondriaOocytesOvarian FollicleOvaryUnfolded Protein ResponseConceptsMitochondrial unfolded protein responseUnfolded mitochondrial proteinsCaseinolytic peptidase PAbsence of ClpPUnfolded protein responsePre-implantation embryosExpression of genesOocyte mitochondrial functionTwo-cell embryosProtein homeostasisMTOR inhibitor rapamycinMitochondrial proteinsOocyte competenceClpPProtein responseInhibitor rapamycinMitochondrial functionP-Akt473P-S6KOvarian follicular reserveSmall mitochondriaMTOR pathway activationPathway activationEmbryosP-S6