Multi-scale mitochondrial cristae remodeling links Opa1 downregulation to reduced OXPHOS capacity in aged hearts

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dc.catalogadorgrr
dc.contributor.authorMolina Riquelme, Isidora Elvira
dc.contributor.authorBarrientos Guajardo, Gonzalo Andres
dc.contributor.authorBreitsprecher, Leonhard
dc.contributor.authorGomez Calderon, Wileidy Andrea
dc.contributor.authorDiaz Castro, Francisco Leopoldo
dc.contributor.authorMorris, Silke
dc.contributor.authorCampo Sfeir, Andrea del
dc.contributor.authorGarrido Olivares, Luis Eugenio
dc.contributor.authorVerdejo Pinochet, Hugo
dc.contributor.authorPsathaki, Olympia Ekaterini
dc.contributor.authorBusch, Karin B.
dc.contributor.authorEisner Sagüés, Verónica Raquel
dc.date.accessioned2025-04-24T17:31:06Z
dc.date.available2025-04-24T17:31:06Z
dc.date.issued2025
dc.description.abstractAging is closely associated with cardiovascular diseases, the leading cause of mortality worldwide.Mitochondrial dysfunction is a hallmark of cardiovascular aging because it generates most of the heart's ATP at the cristae, specialized sub-compartments where OXPHOS takes place. In this study, we used multiple-scale electron microscopy approaches to evaluate age-related mitochondrial and cristaeultrastructural alterations in human and mouse hearts. We found that aged patients’ hearts displayed reduced cristae density as seen by TEM, even before any significant decline in the expression of cristae-shaping proteins. Similarly, a multi-scale approach that included SBF-SEM and TEM showed that in aged mice’s hearts cristae undergo ultrastructural remodeling processes, resulting in a decrease in cristae density and width. Electron tomography suggests an apparent decline in cristae connectivity, and an increase in fenestration size. These changes were linked to Opa1 downregulation, accompanied by reduced OXPHOS maximal respiration, but unrelated to alterations in the levels of OXPHOS core subunits and ATP synthase assembly. Altogether, this indicates that alterations in cristae structure alone are sufficient to impair oxidative metabolism, which highlights its potential as an early signal of cardiac aging, even before noticeable changes in mitochondrial morphology occur.
dc.format.extent41 páginas
dc.fuente.origenORCID
dc.identifier.doi10.1101/2025.04.01.644555
dc.identifier.urihttps://doi.org/10.1101/2025.04.01.644555
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/103435
dc.information.autorucFacultad de Ciencias Biológicas; Molina Riquelme, Isidora Elvira; 0000-0002-0229-8512; 1126907
dc.information.autorucFacultad de Ciencias Biológicas; Barrientos Guajardo, Gonzalo Andres; 0009-0000-3111-7912; 1066781
dc.information.autorucS/I; Gomez Calderon, Wileidy Andrea; S/I; 1218887
dc.information.autorucFacultad de Ciencias Biológicas; Diaz Castro, Francisco Leopoldo; 0000-0003-1644-8742; 1183154
dc.information.autorucEscuela de Química; Campo Sfeir, Andrea del; 0000-0003-3830-7334; 1099680
dc.information.autorucEscuela de Medicina; Garrido Olivares, Luis Eugenio; S/I; 1391
dc.information.autorucEscuela de Medicina; Verdejo Pinochet, Hugo; 0000-0003-0078-4792; 1001175
dc.information.autorucFacultad de Ciencias Biológicas; Eisner Sagüés, Verónica Raquel; 0000-0002-9458-7150; 238175
dc.language.isoen
dc.nota.accesocontenido parcial
dc.revistabioRxiv
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.titleMulti-scale mitochondrial cristae remodeling links Opa1 downregulation to reduced OXPHOS capacity in aged hearts
dc.typepreprint
sipa.codpersvinculados1126907
sipa.codpersvinculados1066781
sipa.codpersvinculados1218887
sipa.codpersvinculados1183154
sipa.codpersvinculados1099680
sipa.codpersvinculados1391
sipa.codpersvinculados1001175
sipa.codpersvinculados238175
sipa.trazabilidadORCID;2025-04-21
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