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Aberrant mitochondrial fission in neurons induced by protein kinase Cδ under oxidative stress conditions in vivo
Neuronal cell death in a number of neurological disorders is associated with aberrant mitochondrial dynamics and mitochondrial degeneration. However, the triggers for this mitochondrial dysregulation are not known. Here we show excessive mitochondrial fission and mitochondrial structural disarray in...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3020920/ https://www.ncbi.nlm.nih.gov/pubmed/21119009 http://dx.doi.org/10.1091/mbc.E10-06-0551 |
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author | Qi, Xin Disatnik, Marie-Helene Shen, Ning Sobel, Raymond A. Mochly-Rosen, Daria |
author_facet | Qi, Xin Disatnik, Marie-Helene Shen, Ning Sobel, Raymond A. Mochly-Rosen, Daria |
author_sort | Qi, Xin |
collection | PubMed |
description | Neuronal cell death in a number of neurological disorders is associated with aberrant mitochondrial dynamics and mitochondrial degeneration. However, the triggers for this mitochondrial dysregulation are not known. Here we show excessive mitochondrial fission and mitochondrial structural disarray in brains of hypertensive rats with hypertension-induced brain injury (encephalopathy). We found that activation of protein kinase Cδ (PKCδ) induced aberrant mitochondrial fragmentation and impaired mitochondrial function in cultured SH-SY5Y neuronal cells and in this rat model of hypertension-induced encephalopathy. Immunoprecipitation studies indicate that PKCδ binds Drp1, a major mitochondrial fission protein, and phosphorylates Drp1 at Ser 579, thus increasing mitochondrial fragmentation. Further, we found that Drp1 Ser 579 phosphorylation by PKCδ is associated with Drp1 translocation to the mitochondria under oxidative stress. Importantly, inhibition of PKCδ, using a selective PKCδ peptide inhibitor (δV1-1), reduced mitochondrial fission and fragmentation and conferred neuronal protection in vivo and in culture. Our study suggests that PKCδ activation dysregulates the mitochondrial fission machinery and induces aberrant mitochondrial fission, thus contributing to neurological pathology. |
format | Text |
id | pubmed-3020920 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-30209202011-03-30 Aberrant mitochondrial fission in neurons induced by protein kinase Cδ under oxidative stress conditions in vivo Qi, Xin Disatnik, Marie-Helene Shen, Ning Sobel, Raymond A. Mochly-Rosen, Daria Mol Biol Cell Articles Neuronal cell death in a number of neurological disorders is associated with aberrant mitochondrial dynamics and mitochondrial degeneration. However, the triggers for this mitochondrial dysregulation are not known. Here we show excessive mitochondrial fission and mitochondrial structural disarray in brains of hypertensive rats with hypertension-induced brain injury (encephalopathy). We found that activation of protein kinase Cδ (PKCδ) induced aberrant mitochondrial fragmentation and impaired mitochondrial function in cultured SH-SY5Y neuronal cells and in this rat model of hypertension-induced encephalopathy. Immunoprecipitation studies indicate that PKCδ binds Drp1, a major mitochondrial fission protein, and phosphorylates Drp1 at Ser 579, thus increasing mitochondrial fragmentation. Further, we found that Drp1 Ser 579 phosphorylation by PKCδ is associated with Drp1 translocation to the mitochondria under oxidative stress. Importantly, inhibition of PKCδ, using a selective PKCδ peptide inhibitor (δV1-1), reduced mitochondrial fission and fragmentation and conferred neuronal protection in vivo and in culture. Our study suggests that PKCδ activation dysregulates the mitochondrial fission machinery and induces aberrant mitochondrial fission, thus contributing to neurological pathology. The American Society for Cell Biology 2011-01-15 /pmc/articles/PMC3020920/ /pubmed/21119009 http://dx.doi.org/10.1091/mbc.E10-06-0551 Text en © 2011 Qi et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,“ “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Qi, Xin Disatnik, Marie-Helene Shen, Ning Sobel, Raymond A. Mochly-Rosen, Daria Aberrant mitochondrial fission in neurons induced by protein kinase Cδ under oxidative stress conditions in vivo |
title | Aberrant mitochondrial fission in neurons induced by protein kinase Cδ under oxidative stress conditions in vivo |
title_full | Aberrant mitochondrial fission in neurons induced by protein kinase Cδ under oxidative stress conditions in vivo |
title_fullStr | Aberrant mitochondrial fission in neurons induced by protein kinase Cδ under oxidative stress conditions in vivo |
title_full_unstemmed | Aberrant mitochondrial fission in neurons induced by protein kinase Cδ under oxidative stress conditions in vivo |
title_short | Aberrant mitochondrial fission in neurons induced by protein kinase Cδ under oxidative stress conditions in vivo |
title_sort | aberrant mitochondrial fission in neurons induced by protein kinase cδ under oxidative stress conditions in vivo |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3020920/ https://www.ncbi.nlm.nih.gov/pubmed/21119009 http://dx.doi.org/10.1091/mbc.E10-06-0551 |
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