Inner mitochondrial membrane structure and fusion dynamics are altered in senescent human iPSC-derived and primary rat cardiomyocytes
DC Element | Wert | Sprache |
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dc.contributor.author | Morris, Silke | |
dc.contributor.author | Molina-Riquelme, Isidora | |
dc.contributor.author | Barrientos, Gonzalo | |
dc.contributor.author | Bravo, Francisco | |
dc.contributor.author | Aedo, Geraldine | |
dc.contributor.author | Gomez, Wileidy | |
dc.contributor.author | Lagos, Daniel | |
dc.contributor.author | Verdejo, Hugo | |
dc.contributor.author | Peischard, Stefan | |
dc.contributor.author | Seebohm, Guiscard | |
dc.contributor.author | Psathaki, Olympia Ekaterini | |
dc.contributor.author | Eisner, Veronica | |
dc.contributor.author | Busch, Karin B. | |
dc.date.accessioned | 2023-07-12T06:57:11Z | - |
dc.date.available | 2023-07-12T06:57:11Z | - |
dc.date.issued | 2023 | |
dc.identifier.issn | 0005-2728 | |
dc.identifier.uri | http://osnascholar.ub.uni-osnabrueck.de/handle/unios/71974 | - |
dc.description.abstract | Dysfunction of the aging heart is a major cause of death in the human population. Amongst other tasks, mito-chondria are pivotal to supply the working heart with ATP. The mitochondrial inner membrane (IMM) ultra -structure 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 beta-galactosidase activity, possess enlarged nuclei, and show p21 upregulation. Most importantly, they also display a compromised inner mito-chondrial 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.sponsorship | BMBF/DLR [FKZ 01DN19046]; PCI/ANID-BMBF [180060]; FONDECYT [1191770]; ANID [21201041, 21191304]; The study was supported by a grant from the BMBF/DLR (FKZ 01DN19046) for S.M./K.B., and PCI/ANID-BMBF (180060) for V.E./H. V./F.B./W.G. and FONDECYT (1191770) for V.E. I.M.-R. and D.L. were supported by ANID Ph.D. fellowships 21201041 and 21191304, respectively. | |
dc.language.iso | en | |
dc.publisher | ELSEVIER | |
dc.relation.ispartof | BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS | |
dc.subject | ATP SYNTHASE | |
dc.subject | Biochemistry & Molecular Biology | |
dc.subject | Biophysics | |
dc.subject | CARDIOLIPIN | |
dc.subject | Cardiomyocytes | |
dc.subject | CELLULAR SENESCENCE | |
dc.subject | COMPLEX-I | |
dc.subject | CRISTAE | |
dc.subject | Cristae structure | |
dc.subject | DOXORUBICIN | |
dc.subject | Inner mitochondrial membrane dynamics | |
dc.subject | Mitochondrial fusion and fission dynamics | |
dc.subject | MOLECULAR-BASIS | |
dc.subject | OXIDATIVE-PHOSPHORYLATION | |
dc.subject | RESPIRATORY-CHAIN | |
dc.subject | Senescence | |
dc.subject | STRESS | |
dc.title | Inner mitochondrial membrane structure and fusion dynamics are altered in senescent human iPSC-derived and primary rat cardiomyocytes | |
dc.type | journal article | |
dc.identifier.doi | 10.1016/j.bbabio.2022.148949 | |
dc.identifier.isi | ISI:000995579600001 | |
dc.description.volume | 1864 | |
dc.description.issue | 2 | |
dc.contributor.orcid | http://orcid.org/0000-0002-9458-7150 | |
dc.contributor.orcid | http://orcid.org/0000-0002-3980-6365 | |
dc.contributor.orcid | http://orcid.org/0000-0003-2609-5397 | |
dc.contributor.orcid | http://orcid.org/0000-0003-0078-4792 | |
dc.contributor.researcherid | ISS-7416-2023 | |
dc.identifier.eissn | 1879-2650 | |
dc.publisher.place | RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS | |
dcterms.isPartOf.abbreviation | Biochim. Biophys. Acta-Bioenerg. | |
dcterms.oaStatus | hybrid | |
local.import.remains | affiliations : University of Munster; Pontificia Universidad Catolica de Chile; Pontificia Universidad Catolica de Chile; University of Munster; University Osnabruck | |
local.import.remains | earlyaccessdate : DEC 2022 | |
local.import.remains | web-of-science-index : Science Citation Index Expanded (SCI-EXPANDED) | |
crisitem.author.dept | FB 05 - Biologie/Chemie | - |
crisitem.author.deptid | fb05 | - |
crisitem.author.orcid | 0000-0002-4035-6840 | - |
crisitem.author.parentorg | Universität Osnabrück | - |
crisitem.author.netid | PsOl764 | - |
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geprüft am 09.06.2024