Inner mitochondrial membrane structure and fusion dynamics are altered in senescent human iPSC-derived and primary rat cardiomyocytes

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dc.article.number148949
dc.catalogadorjwg
dc.contributor.authorMorris, Silke
dc.contributor.authorBusch, Karin B.
dc.contributor.authorMolina Riquelme, Isidora
dc.contributor.authorBarrientos, Gonzalo
dc.contributor.authorBravo, Francisco
dc.contributor.authorAedo, Geraldine
dc.contributor.authorGómez, Wileidy
dc.contributor.authorLagos, Daniel
dc.contributor.authorEisner Sagues Veronica Raquel
dc.contributor.authorVerdejo, Hugo
dc.contributor.authorPeischard, Stefan
dc.contributor.authorSeebohm, Guiscard
dc.contributor.authorPsathaki, Olympia E.
dc.date.accessioned2024-01-26T18:05:11Z
dc.date.available2024-01-26T18:05:11Z
dc.date.issued2023
dc.description.abstractDysfunction of the aging heart is a major cause of death in the human population. Amongst other tasks, mitochondria are pivotal to supply the working heart with ATP. The mitochondrial inner membrane (IMM) ultrastructure is tailored to meet these demands and to provide nano-compartments for specific tasks. Thus, function and morphology are closely coupled. Senescent cardiomyocytes from the mouse heart display alterations of the inner mitochondrial membrane. To study the relation between inner mitochondrial membrane architecture, dynamics and function is hardly possible in living organisms. Here, we present two cardiomyocyte senescence cell models that allow in cellular studies of mitochondrial performance. We show that doxorubicin treatment transforms human iPSC-derived cardiomyocytes and rat neonatal cardiomyocytes in an aged phenotype. The treated cardiomyocytes display double-strand breaks in the nDNA, have ?-galactosidase activity, possess enlarged nuclei, and show p21 upregulation. Most importantly, they also display a compromised inner mitochondrial structure. This prompted us to test whether the dynamics of the inner membrane was also altered. We found that the exchange of IMM components after organelle fusion was faster in doxorubicin-treated cells than in control cells, with no change in mitochondrial fusion dynamics at the meso-scale. Such altered IMM morphology and dynamics may have important implications for local OXPHOS protein organization, exchange of damaged components, and eventually the mitochondrial bioenergetics function of the aged cardiomyocyte.
dc.description.funderImaging Network of the University of Münster
dc.description.funderPCI
dc.description.funderBMBF
dc.description.funderFONDECYT
dc.description.funderDLR
dc.description.funderANID
dc.identifier.doi10.1016/j.bbabio.2022.148949
dc.identifier.eissn18792650
dc.identifier.issn18792650 00052728
dc.identifier.pubmedid36493857
dc.identifier.scopusidSCOPUS_ID:85143878558
dc.identifier.uriwww.elsevier.com/locate/bbabio
dc.identifier.urihttps://doi.org/10.1016/j.bbabio.2022.148949
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/80994
dc.information.autorucFacultad de Ciencias Biológicas; Eisner Sagues Veronica Raquel; 0000-0002-9458-7150; 238175
dc.issue.numero2
dc.language.isoen
dc.nota.accesoContenido parcial
dc.publisherElsevier B.V.
dc.relation.ispartofBiochimica et Biophysica Acta - Bioenergetics
dc.revistaBiochimica et Biophysica Acta - Bioenergetics
dc.rightsacceso restringido
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.titleInner mitochondrial membrane structure and fusion dynamics are altered in senescent human iPSC-derived and primary rat cardiomyocytes
dc.typeartículo
dc.volumen1864
sipa.codpersvinculados238175
sipa.trazabilidadORCID;2024-01-15
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