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Defective sarcoplasmic reticulum-mitochondria calcium exchange in aged mouse myocardium
Fernandez-Sanz, C (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Ruiz-Meana, M (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Miro-Casas, E (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Nuñez, E (Centro Nacional de Investigaciones Cardiovasculares)
Castellano, J (Cardiología, Hospital Universitari Vall d'Hebron, Institut de Recerca, Universitat Autònoma de Barcelona)
Loureiro, M (Centro Nacional de Investigaciones Cardiovasculares)
Barba, I (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Poncelas, M (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Rodriguez-Sinovas, A (CHospital Universitari Vall d'Hebron. Institut de Recerca)
Vázquez, J (Centro Nacional de Investigaciones Cardiovasculares)
Garcia-Dorado, D (CHospital Universitari Vall d'Hebron. Institut de Recerca)
Universitat Autònoma de Barcelona

Date: 2014
Abstract: Mitochondrial alterations are critically involved in increased vulnerability to disease during aging. We investigated the contribution of mitochondria-sarcoplasmic reticulum (SR) communication in cardiomyocyte functional alterations during aging. Heart function (echocardiography) and ATP/phosphocreatine (NMR spectroscopy) were preserved in hearts from old mice (>20 months) with respect to young mice (5-6 months). Mitochondrial membrane potential and resting O consumption were similar in mitochondria from young and old hearts. However, maximal ADP-stimulated O consumption was specifically reduced in interfibrillar mitochondria from aged hearts. Second generation proteomics disclosed an increased mitochondrial protein oxidation in advanced age. Because energy production and oxidative status are regulated by mitochondrial Ca 2+, we investigated the effect of age on mitochondrial Ca 2+ uptake. Although no age-dependent differences were found in Ca 2+ uptake kinetics in isolated mitochondria, mitochondrial Ca 2+ uptake secondary to SR Ca 2+ release was significantly reduced in cardiomyocytes from old hearts, and this effect was associated with decreased NAD(P)H regeneration and increased mitochondrial ROS upon increased contractile activity. Immunofluorescence and proximity ligation assay identified the defective communication between mitochondrial voltage-dependent anion channel and SR ryanodine receptor (RyR) in cardiomyocytes from aged hearts associated with altered Ca 2+ handling. Age-dependent alterations in SR Ca 2+ transfer to mitochondria and in Ca 2+ handling could be reproduced in cardiomyoctes from young hearts after interorganelle disruption with colchicine, at concentrations that had no effect in aged cardiomyocytes or isolated mitochondria. Thus, defective SR-mitochondria communication underlies inefficient interorganelle Ca 2+ exchange that contributes to energy demand/supply mistmach and oxidative stress in the aged heart.
Note: Número d'acord de subvenció MICINN/SAF2008-03067
Note: Número d'acord de subvenció ISCIII/RD12-0042-0021
Rights: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Language: Anglès
Document: article ; recerca ; publishedVersion
Published in: Cell death and disease, Vol. 5 (december 2014) , p. e1573, ISSN 2041-4889

DOI: 10.1038/cddis.2014.526
PMID: 25522267

15 p, 2.3 MB

The record appears in these collections:
Articles > Research articles
Articles > Published articles

 Record created 2018-01-29, last modified 2020-08-09

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