Daño Mitocondrial

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Rev Esp Cardiol. 2011;64(10):916–923

Review article

Mitochondrial Dynamics: a Potential New Therapeutic Target for Heart Failure
´ Jovan Kuzmicic,a Andrea del Campo,a Camila Lopez-Crisosto,a Pablo E.Morales,a Christian Pennanen,a Roberto Bravo-Sagua,a Jonathan Hechenleitner,a Ramiro Zepeda,a Pablo F. Castro,a Hugo E. Verdejo,a,b Valentina Parra,a Mario Chiong,a and Sergio Lavanderoa,c,*
a b c

´lula, Facultad de Ciencias Quı´micas y Farmace ´uticas, Universidad de Chile, Santiago, Chile Centro Estudios Moleculares de la Ce ´lica de Chile, Santiago, Chile Departamento de EnfermedadesCardiovasculares, Facultad de Medicina, Pontificia Universidad Cato ´dicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile Instituto de Ciencias Biome

Article history: Available online 5 August 2011 Keywords: Cardiac metabolism Mitochondria Mitochondrial dynamics Heart failure

ABSTRACT

Mitochondria are dynamic organelles able to vary their morphology between elongated interconnectedmitochondrial networks and fragmented disconnected arrays, through events of mitochondrial fusion and fission, respectively. These events allow the transmission of signaling messengers and exchange of metabolites within the cell. They have also been implicated in a variety of biological processes including embryonic development, metabolism, apoptosis, and autophagy. Although the majority of thesestudies have been confined to noncardiac cells, emerging evidence suggests that changes in mitochondrial morphology could participate in cardiac development, the response to ischemia-reperfusion injury, heart failure, and diabetes mellitus. In this article, we review how the mitochondrial dynamics are altered in different cardiac pathologies, with special emphasis on heart failure, and how this knowledgemay provide new therapeutic targets for treating cardiovascular diseases. ´ ˜ ˜ ß 2011 Sociedad Espanola de Cardiologıa. Published by Elsevier Espana, S.L. All rights reserved.

´ ´ Dinamica mitocondrial: un potencial nuevo blanco terapeutico para la insuficiencia cardiaca
RESUMEN

Palabras clave: Metabolismo cardiaco Mitocondria ´ Dinamica mitocondrial Insuficiencia cardiaca

´ ´ Lasmitocondrias son organelos dinamicos, capaces de intercambiar su morfologıa entre redes elongadas ´ ´ e interconectadas y arreglos fragmentados y desconectados mediante los procesos de fusion y fision ´ ´ ´ ˜ mitocondrial, respectivamente. Estos eventos permiten la transmision de moleculas de senalizacion y el ´ intercambio de metabolitos dentro de la celula y participan en una amplia variedad deprocesos ´ biologicos, que incluyen el desarrollo embrionario, el metabolismo, la apoptosis y la autofagia. Aunque la ´ ´ mayorıa de estos estudios se han realizado en celulas no cardiacas, la evidencia emergente indica que los ´ ˜ cambios en la morfologıa mitocondrial participan en el desarrollo cardiaco, la respuesta al dano por ´ ´ ´ isquemia-reperfusion, la insuficiencia cardiaca y la diabetesmellitus. En este artıculo se revisa como ´ ´ la dinamica mitocondrial se altera en diversas enfermedades cardiacas, con especial enfasis en la ´ ´ ´ insuficiencia cardiaca, y como este conocimiento podrıa proporcionar nuevos blancos terapeuticos para su tratamiento. ´ ˜ ˜ ß 2011 Sociedad Espanola de Cardiologıa. Publicado por Elsevier Espana, S.L. Todos los derechos reservados.

INTRODUCTION Heartfailure is a complex condition characterized by the inability of the heart to provide an adequate cardiac output to match the metabolic demands of the remaining tissues. The condition represents the terminal phase of ischemic heart disease, valve disease, and hypertensive conditions.1 In industrialized countries, where the life expectancy of the population and survival after other heart diseases...