Involvement of Oxidative Stress in Mitochondrial Abnormalities During the Development of Heart Disease

<b>Background:</b> Several mitochondrial abnormalities such as defective energy production, depletion of energy stores, Ca<sup>2+</sup> accumulation, generation of reactive oxygen species, and impaired intracellular signaling are associated with cardiac dysfunction during the...

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Main Authors: Naranjan S. Dhalla, Petr Ostadal, Paramjit S. Tappia
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/13/6/1338
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author Naranjan S. Dhalla
Petr Ostadal
Paramjit S. Tappia
author_facet Naranjan S. Dhalla
Petr Ostadal
Paramjit S. Tappia
author_sort Naranjan S. Dhalla
collection DOAJ
description <b>Background:</b> Several mitochondrial abnormalities such as defective energy production, depletion of energy stores, Ca<sup>2+</sup> accumulation, generation of reactive oxygen species, and impaired intracellular signaling are associated with cardiac dysfunction during the development of different heart diseases. <b>Methods:</b> A narrative review was compiled by a search for applicable literature in MEDLINE via PubMed. <b>Results:</b> Mitochondria generate ATP through the processes of electron transport and oxidative phosphorylation, which is used as energy for cardiac contractile function. Mitochondria, in fact, are the key subcellular organelle for the regulation of intracellular Ca<sup>2+</sup> concentration and are considered to serve as a buffer to maintain Ca<sup>2+</sup> homeostasis in cardiomyocytes. However, during the development of heart disease, the excessive accumulation of intracellular Ca<sup>2+</sup> results in mitochondria Ca<sup>2+</sup>-overload, which, in turn, impairs mitochondrial energy production and induces cardiac dysfunction. Mitochondria also generate reactive oxygen species (ROS), including superoxide anion radicals and hydroxyl radicals as well as non-radical oxidants such as hydrogen peroxide, which promote lipid peroxidation and the subsequent disturbance of Ca<sup>2+</sup> homeostasis, cellular damage, and death. <b>Conclusion:</b> These observations support the view that both oxidative stress and intracellular Ca<sup>2+</sup>-overload play a critical role in mitochondrial disruption during the pathogenesis of different cardiac pathologies.
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spelling doaj-art-f8b7af9e3df54c828200fed08c8a25102025-08-20T03:27:13ZengMDPI AGBiomedicines2227-90592025-05-01136133810.3390/biomedicines13061338Involvement of Oxidative Stress in Mitochondrial Abnormalities During the Development of Heart DiseaseNaranjan S. Dhalla0Petr Ostadal1Paramjit S. Tappia2St. Boniface Hospital Albrechtsen Research Centre, Institute of Cardiovascular Sciences, Department of Physiology & Pathophysiology, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R2H 2A6, CanadaDepartment of Cardiology, 2nd Faculty of Medicine, Charles University, Motol University Hospital, V Uvalu 84, 15000 Prague, Czech RepublicAsper Clinical Research Institute, St. Boniface Hospital, Winnipeg, MB R2H 2A6, Canada<b>Background:</b> Several mitochondrial abnormalities such as defective energy production, depletion of energy stores, Ca<sup>2+</sup> accumulation, generation of reactive oxygen species, and impaired intracellular signaling are associated with cardiac dysfunction during the development of different heart diseases. <b>Methods:</b> A narrative review was compiled by a search for applicable literature in MEDLINE via PubMed. <b>Results:</b> Mitochondria generate ATP through the processes of electron transport and oxidative phosphorylation, which is used as energy for cardiac contractile function. Mitochondria, in fact, are the key subcellular organelle for the regulation of intracellular Ca<sup>2+</sup> concentration and are considered to serve as a buffer to maintain Ca<sup>2+</sup> homeostasis in cardiomyocytes. However, during the development of heart disease, the excessive accumulation of intracellular Ca<sup>2+</sup> results in mitochondria Ca<sup>2+</sup>-overload, which, in turn, impairs mitochondrial energy production and induces cardiac dysfunction. Mitochondria also generate reactive oxygen species (ROS), including superoxide anion radicals and hydroxyl radicals as well as non-radical oxidants such as hydrogen peroxide, which promote lipid peroxidation and the subsequent disturbance of Ca<sup>2+</sup> homeostasis, cellular damage, and death. <b>Conclusion:</b> These observations support the view that both oxidative stress and intracellular Ca<sup>2+</sup>-overload play a critical role in mitochondrial disruption during the pathogenesis of different cardiac pathologies.https://www.mdpi.com/2227-9059/13/6/1338mitochondriaoxidative stressCa<sup>2+</sup>-handling defectscell deathcardiac dysfunctionheart disease
spellingShingle Naranjan S. Dhalla
Petr Ostadal
Paramjit S. Tappia
Involvement of Oxidative Stress in Mitochondrial Abnormalities During the Development of Heart Disease
Biomedicines
mitochondria
oxidative stress
Ca<sup>2+</sup>-handling defects
cell death
cardiac dysfunction
heart disease
title Involvement of Oxidative Stress in Mitochondrial Abnormalities During the Development of Heart Disease
title_full Involvement of Oxidative Stress in Mitochondrial Abnormalities During the Development of Heart Disease
title_fullStr Involvement of Oxidative Stress in Mitochondrial Abnormalities During the Development of Heart Disease
title_full_unstemmed Involvement of Oxidative Stress in Mitochondrial Abnormalities During the Development of Heart Disease
title_short Involvement of Oxidative Stress in Mitochondrial Abnormalities During the Development of Heart Disease
title_sort involvement of oxidative stress in mitochondrial abnormalities during the development of heart disease
topic mitochondria
oxidative stress
Ca<sup>2+</sup>-handling defects
cell death
cardiac dysfunction
heart disease
url https://www.mdpi.com/2227-9059/13/6/1338
work_keys_str_mv AT naranjansdhalla involvementofoxidativestressinmitochondrialabnormalitiesduringthedevelopmentofheartdisease
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AT paramjitstappia involvementofoxidativestressinmitochondrialabnormalitiesduringthedevelopmentofheartdisease