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http://hdl.handle.net/10261/269484
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dc.contributor.author | Del Rey, Manuel J. | - |
dc.contributor.author | Meroño, Carolina | - |
dc.contributor.author | Municio, Cristina | - |
dc.contributor.author | Mittelbrunn, María | - |
dc.contributor.author | García-Consuegra, Inés | - |
dc.contributor.author | Criado, Gabriel | - |
dc.contributor.author | Pablos, José L. | - |
dc.date.accessioned | 2022-05-12T11:30:03Z | - |
dc.date.available | 2022-05-12T11:30:03Z | - |
dc.date.issued | 2021-07-15 | - |
dc.identifier | doi: 10.1242/dmm.048995 | - |
dc.identifier | issn: 1754-8411 | - |
dc.identifier.citation | DMM Disease Models and Mechanisms 14 (2021) | - |
dc.identifier.uri | http://hdl.handle.net/10261/269484 | - |
dc.description.abstract | Mitochondrial dysfunction associates with several pathological processes and contributes to chronic inflammatory and ageing-related diseases. Mitochondrial transcription factor A (TFAM) plays a critical role in maintaining mtDNA integrity and function. Taking advantage of Tfam UBC-Cre/ER mice to investigate mitochondrial dysfunction in the stromal cell component, we describe an inducible in vitro model of mitochondrial dysfunction by stable depletion of TFAM in primary mouse skin fibroblasts (SK-FBs) after 4-hydroxytamoxifen (4-OHT) administration. Tfam gene deletion caused a sustained reduction in Tfam and mtDNA-encoded mRNA in Cre(+) SK-FBs cultured for low (LP) and high (HP) passages that translated into a loss of TFAM protein. TFAM depletion led to a substantial reduction in mitochondrial respiratory chain complexes that was exacerbated in HP SK-FB cultures. The assembly pattern showed that the respiratory complexes fail to reach the respirasome in 4-OHT-treated Cre(+) SK-FBs. Functionally, mito-stress and glycolysis-stress tests showed that mitochondrial dysfunction developed after long-term 4-OHT treatment in HP Cre(+) SK-FBs and was compensated by an increase in the glycolytic capacity. Finally, expression analysis revealed that 4-OHT-treated HP Cre(+) SK-FBs showed a senescent and pro-inflammatory phenotype. | - |
dc.description.sponsorship | Fondo de Investigación Sanitaria, Instituto de Salud Carlos III (FIS16/00032, FIS19/01129 and RETICS RD16/0012), co-financed by the European Regional Development Fund, and the Ministerio de Economı́a y Competitividad Juan de la Cierva Program (IJCI-2016-27666) | - |
dc.language | eng | - |
dc.relation.isversionof | Publisher's version | - |
dc.rights | openAccess | - |
dc.subject | TFAM | - |
dc.subject | Mitochondrial dysfunction | - |
dc.subject | Fibroblasts | - |
dc.subject | Inflammation | - |
dc.subject | Cellular senescence | - |
dc.title | TFAM-deficient mouse skin fibroblasts – an ex vivo model of mitochondrial dysfunction | - |
dc.type | artículo | - |
dc.identifier.doi | 10.1242/dmm.048995 | - |
dc.relation.publisherversion | http://dx.doi.org/10.1242/dmm.048995 | - |
dc.date.updated | 2022-05-12T11:30:04Z | - |
dc.rights.license | https://creativecommons.org/licenses/by/4.0/ | - |
dc.contributor.funder | Instituto de Salud Carlos III | - |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | - |
dc.relation.csic | Sí | - |
dc.identifier.funder | http://dx.doi.org/10.13039/501100004587 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100003329 | es_ES |
dc.type.coar | http://purl.org/coar/resource_type/c_6501 | es_ES |
item.grantfulltext | open | - |
item.openairetype | artículo | - |
item.cerifentitytype | Publications | - |
item.fulltext | With Fulltext | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
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MittelbrunnMTFAM-deficientMouse.pdf | 2,95 MB | Adobe PDF | Visualizar/Abrir |
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