2024
Mitochondria as determinants of reproductive senescence and competence: implications for diagnosis of embryo competence in assisted reproduction
Yildirim R, Seli E. Mitochondria as determinants of reproductive senescence and competence: implications for diagnosis of embryo competence in assisted reproduction. Human Reproduction 2024, 39: 2160-2170. PMID: 39066612, DOI: 10.1093/humrep/deae171.Peer-Reviewed Original ResearchMultiple quality control mechanismsMitochondrial unfolded protein responseMitochondrial DNA copy numberUnfolded protein responseQuality control mechanismsDNA copy numberMitochondrial networkRegulate calcium signalingMitochondrial dynamicsReproductive successMitochondrial quantityProtein responseDinucleotide contentModulate apoptosisOxidative phosphorylationCellular pathwaysCopy numberMitochondrial dysfunctionMitochondriaCalcium signalingEmbryo competenceMembrane potentialAssisted reproductionDiagnostic targetsReproductive senescenceDisruption 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 ResearchConceptsCaseinolytic 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 oocytes
2020
Mitochondrial Stress Response Gene Clpp Is Not Required for Granulosa Cell Function
Esencan E, Cozzolino M, Imamoglu G, Seli E. Mitochondrial Stress Response Gene Clpp Is Not Required for Granulosa Cell Function. Antioxidants 2020, 10: 1. PMID: 33374937, PMCID: PMC7821922, DOI: 10.3390/antiox10010001.Peer-Reviewed Original ResearchMitochondrial unfolded protein responseUnfolded mitochondrial proteinsLoss of ClpPGerminal vesicleUnfolded protein responseCell functionCumulus cell functionGranulosa/cumulus cellsMitochondrial proteinsClpP deletionClpPProtein responseGermline deletionMetabolic stressGranulosa cell functionDeletionUPRCumulus cellsMice resultsSimilar numberMII oocytesFemale miceWild-type miceEarly antralCellsImpaired 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 ResearchConceptsMitochondrial 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