2026-05-20T23:32:33Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/55352024-10-31T11:47:14Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Fernandez-Sanz, C.
author
Ruiz-Meana, Marisol
author
Miro-Casas, E.
author
Nunez, Estefania
author
Castellano, J.
author
Loureiro, Marta
author
Barba, Ignasi
author
Poncelas, M.
author
Rodriguez-Sinovas, A.
author
Vazquez, Jesus
author
Garcia-Dorado, David
funder
Ministerio de Ciencia e Innovación (España)
funder
Instituto de Salud Carlos III
funder
Ministerio de Economía y Competitividad (España)
funder
Fundación ProCNIC
2017-12-01T07:37:29Z
2017-12-01T07:37:29Z
2014
Cell Death Dis. 2014; 5:e1573
10.1038/cddis.2014.526
2041-4889
CELL DEATH \& DISEASE
25522267
http://hdl.handle.net/20.500.12105/5535
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 (420 months) with respect to young mice (5-6 months). Mitochondrial membrane potential and resting O-2 consumption were similar in mitochondria from young and old hearts. However, maximal ADP-stimulated O-2 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 Ca2+, we investigated the effect of age on mitochondrial Ca2+ uptake. Although no age-dependent differences were found in Ca2+ uptake kinetics in isolated mitochondria, mitochondrial Ca2+ uptake secondary to SR Ca2+ 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 Ca2+ handling. Age-dependent alterations in SR Ca2+ transfer to mitochondria and in Ca2+ 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 Ca2+ exchange that contributes to energy demand/supply mistmach and oxidative stress in the aged heart.
eng
TRAP MASS-SPECTROMETRY
QUANTITATIVE PROTEOMICS
ENDOPLASMIC-RETICULUM
RYANODINE RECEPTORS
CARDIAC MYOCYTES
OXIDATIVE STRESS
HEART-FAILURE
INTERFIBRILLAR MITOCHONDRIA
PERMEABILITY TRANSITION
REDOX MODIFICATION
Defective sarcoplasmic reticulum-mitochondria calcium exchange in aged mouse myocardium
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