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The Opa1-Dependent Mitochondrial Cristae Remodeling Pathway Controls Atrophic, Apoptotic, and Ischemic Tissue Damage

Mitochondrial morphological and ultrastructural changes occur during apoptosis and autophagy, but whether they are relevant in vivo for tissue response to damage is unclear. Here we investigate the role of the optic atrophy 1 (OPA1)-dependent cristae remodeling pathway in vivo and provide evidence t...

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Autores principales: Varanita, Tatiana, Soriano, Maria Eugenia, Romanello, Vanina, Zaglia, Tania, Quintana-Cabrera, Rubén, Semenzato, Martina, Menabò, Roberta, Costa, Veronica, Civiletto, Gabriele, Pesce, Paola, Viscomi, Carlo, Zeviani, Massimo, Di Lisa, Fabio, Mongillo, Marco, Sandri, Marco, Scorrano, Luca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4457892/
https://www.ncbi.nlm.nih.gov/pubmed/26039448
http://dx.doi.org/10.1016/j.cmet.2015.05.007
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author Varanita, Tatiana
Soriano, Maria Eugenia
Romanello, Vanina
Zaglia, Tania
Quintana-Cabrera, Rubén
Semenzato, Martina
Menabò, Roberta
Costa, Veronica
Civiletto, Gabriele
Pesce, Paola
Viscomi, Carlo
Zeviani, Massimo
Di Lisa, Fabio
Mongillo, Marco
Sandri, Marco
Scorrano, Luca
author_facet Varanita, Tatiana
Soriano, Maria Eugenia
Romanello, Vanina
Zaglia, Tania
Quintana-Cabrera, Rubén
Semenzato, Martina
Menabò, Roberta
Costa, Veronica
Civiletto, Gabriele
Pesce, Paola
Viscomi, Carlo
Zeviani, Massimo
Di Lisa, Fabio
Mongillo, Marco
Sandri, Marco
Scorrano, Luca
author_sort Varanita, Tatiana
collection PubMed
description Mitochondrial morphological and ultrastructural changes occur during apoptosis and autophagy, but whether they are relevant in vivo for tissue response to damage is unclear. Here we investigate the role of the optic atrophy 1 (OPA1)-dependent cristae remodeling pathway in vivo and provide evidence that it regulates the response of multiple tissues to apoptotic, necrotic, and atrophic stimuli. Genetic inhibition of the cristae remodeling pathway in vivo does not affect development, but protects mice from denervation-induced muscular atrophy, ischemic heart and brain damage, as well as hepatocellular apoptosis. Mechanistically, OPA1-dependent mitochondrial cristae stabilization increases mitochondrial respiratory efficiency and blunts mitochondrial dysfunction, cytochrome c release, and reactive oxygen species production. Our results indicate that the OPA1-dependent cristae remodeling pathway is a fundamental, targetable determinant of tissue damage in vivo.
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spelling pubmed-44578922015-06-14 The Opa1-Dependent Mitochondrial Cristae Remodeling Pathway Controls Atrophic, Apoptotic, and Ischemic Tissue Damage Varanita, Tatiana Soriano, Maria Eugenia Romanello, Vanina Zaglia, Tania Quintana-Cabrera, Rubén Semenzato, Martina Menabò, Roberta Costa, Veronica Civiletto, Gabriele Pesce, Paola Viscomi, Carlo Zeviani, Massimo Di Lisa, Fabio Mongillo, Marco Sandri, Marco Scorrano, Luca Cell Metab Article Mitochondrial morphological and ultrastructural changes occur during apoptosis and autophagy, but whether they are relevant in vivo for tissue response to damage is unclear. Here we investigate the role of the optic atrophy 1 (OPA1)-dependent cristae remodeling pathway in vivo and provide evidence that it regulates the response of multiple tissues to apoptotic, necrotic, and atrophic stimuli. Genetic inhibition of the cristae remodeling pathway in vivo does not affect development, but protects mice from denervation-induced muscular atrophy, ischemic heart and brain damage, as well as hepatocellular apoptosis. Mechanistically, OPA1-dependent mitochondrial cristae stabilization increases mitochondrial respiratory efficiency and blunts mitochondrial dysfunction, cytochrome c release, and reactive oxygen species production. Our results indicate that the OPA1-dependent cristae remodeling pathway is a fundamental, targetable determinant of tissue damage in vivo. Cell Press 2015-06-02 /pmc/articles/PMC4457892/ /pubmed/26039448 http://dx.doi.org/10.1016/j.cmet.2015.05.007 Text en © 2015 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Varanita, Tatiana
Soriano, Maria Eugenia
Romanello, Vanina
Zaglia, Tania
Quintana-Cabrera, Rubén
Semenzato, Martina
Menabò, Roberta
Costa, Veronica
Civiletto, Gabriele
Pesce, Paola
Viscomi, Carlo
Zeviani, Massimo
Di Lisa, Fabio
Mongillo, Marco
Sandri, Marco
Scorrano, Luca
The Opa1-Dependent Mitochondrial Cristae Remodeling Pathway Controls Atrophic, Apoptotic, and Ischemic Tissue Damage
title The Opa1-Dependent Mitochondrial Cristae Remodeling Pathway Controls Atrophic, Apoptotic, and Ischemic Tissue Damage
title_full The Opa1-Dependent Mitochondrial Cristae Remodeling Pathway Controls Atrophic, Apoptotic, and Ischemic Tissue Damage
title_fullStr The Opa1-Dependent Mitochondrial Cristae Remodeling Pathway Controls Atrophic, Apoptotic, and Ischemic Tissue Damage
title_full_unstemmed The Opa1-Dependent Mitochondrial Cristae Remodeling Pathway Controls Atrophic, Apoptotic, and Ischemic Tissue Damage
title_short The Opa1-Dependent Mitochondrial Cristae Remodeling Pathway Controls Atrophic, Apoptotic, and Ischemic Tissue Damage
title_sort opa1-dependent mitochondrial cristae remodeling pathway controls atrophic, apoptotic, and ischemic tissue damage
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4457892/
https://www.ncbi.nlm.nih.gov/pubmed/26039448
http://dx.doi.org/10.1016/j.cmet.2015.05.007
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