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The path from mitochondrial ROS to aging runs through the mitochondrial permeability transition pore.
Rottenberg, Hagai; Hoek, Jan B.
Afiliação
  • Rottenberg H; New Hope Biomedical R&D, 23 W. Bridge Street, New Hope, PA, 18038, USA.
  • Hoek JB; Department of Anatomy, Pathology and Cell Biology, MitoCare Center, Thomas Jefferson University, Philadelphia, PA, 19107, USA.
Aging Cell ; 16(5): 943-955, 2017 10.
Article em En | MEDLINE | ID: mdl-28758328
Excessive production of mitochondrial reactive oxygen species (mROS) is strongly associated with mitochondrial and cellular oxidative damage, aging, and degenerative diseases. However, mROS also induces pathways of protection of mitochondria that slow aging, inhibit cell death, and increase lifespan. Recent studies show that the activation of the mitochondrial permeability transition pore (mPTP), which is triggered by mROS and mitochondrial calcium overloading, is enhanced in aged animals and humans and in aging-related degenerative diseases. mPTP opening initiates further production and release of mROS that damage both mitochondrial and nuclear DNA, proteins, and phospholipids, and also releases matrix NAD that is hydrolyzed in the intermembrane space, thus contributing to the depletion of cellular NAD that accelerates aging. Oxidative damage to calcium transporters leads to calcium overload and more frequent opening of mPTP. Because aging enhances the opening of the mPTP and mPTP opening accelerates aging, we suggest that mPTP opening drives the progression of aging. Activation of the mPTP is regulated, directly and indirectly, not only by the mitochondrial protection pathways that are induced by mROS, but also by pro-apoptotic signals that are induced by DNA damage. We suggest that the integration of these contrasting signals by the mPTP largely determines the rate of cell aging and the initiation of cell death, and thus animal lifespan. The suggestion that the control of mPTP activation is critical for the progression of aging can explain the conflicting and confusing evidence regarding the beneficial and deleterious effects of mROS on health and lifespan.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Envelhecimento / Traumatismo por Reperfusão / Espécies Reativas de Oxigênio / Doenças Neurodegenerativas / Proteínas de Transporte da Membrana Mitocondrial / Mitocôndrias Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Envelhecimento / Traumatismo por Reperfusão / Espécies Reativas de Oxigênio / Doenças Neurodegenerativas / Proteínas de Transporte da Membrana Mitocondrial / Mitocôndrias Idioma: En Ano de publicação: 2017 Tipo de documento: Article