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SIRT3 interacts with the daf-16 homolog FOXO3a in the Mitochondria, as well as increases FOXO3a Dependent Gene expression
Cellular longevity is a complex process relevant to age-related diseases including but not limited to chronic illness such as diabetes and metabolic syndromes. Two gene families have been shown to play a role in the genetic regulation of longevity; the Sirtuin and FOXO families. It is also establish...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Ivyspring International Publisher
2008
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2532794/ https://www.ncbi.nlm.nih.gov/pubmed/18781224 |
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author | Jacobs, Kristi Muldoon Pennington, J. Daniel Bisht, Kheem S. Aykin-Burns, Nukhet Kim, Hyun-Seok Mishra, Mark Sun, Lunching Nguyen, Phuongmai Ahn, Bong-Hyun Leclerc, Jaime Deng, Chu-Xia Spitz, Douglas R. Gius, David |
author_facet | Jacobs, Kristi Muldoon Pennington, J. Daniel Bisht, Kheem S. Aykin-Burns, Nukhet Kim, Hyun-Seok Mishra, Mark Sun, Lunching Nguyen, Phuongmai Ahn, Bong-Hyun Leclerc, Jaime Deng, Chu-Xia Spitz, Douglas R. Gius, David |
author_sort | Jacobs, Kristi Muldoon |
collection | PubMed |
description | Cellular longevity is a complex process relevant to age-related diseases including but not limited to chronic illness such as diabetes and metabolic syndromes. Two gene families have been shown to play a role in the genetic regulation of longevity; the Sirtuin and FOXO families. It is also established that nuclear Sirtuins interact with and under specific cellular conditions regulate the activity of FOXO gene family proteins. Thus, we hypothesize that a mitochondrial Sirtuin (SIRT3) might also interact with and regulate the activity of the FOXO proteins. To address this we used HCT116 cells overexpressing either wild-type or a catalytically inactive dominant negative SIRT3. For the first time we establish that FOXO3a is also a mitochondrial protein and forms a physical interaction with SIRT3 in mitochondria. Overexpression of a wild-type SIRT3 gene increase FOXO3a DNA-binding activity as well as FOXO3a dependent gene expression. Biochemical analysis of HCT116 cells over expressing the deacetylation mutant, as compared to wild-type SIRT3 gene, demonstrated an overall oxidized intracellular environment, as monitored by increase in intracellular superoxide and oxidized glutathione levels. As such, we propose that SIRT3 and FOXO3a comprise a potential mitochondrial signaling cascade response pathway. |
format | Text |
id | pubmed-2532794 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-25327942008-09-09 SIRT3 interacts with the daf-16 homolog FOXO3a in the Mitochondria, as well as increases FOXO3a Dependent Gene expression Jacobs, Kristi Muldoon Pennington, J. Daniel Bisht, Kheem S. Aykin-Burns, Nukhet Kim, Hyun-Seok Mishra, Mark Sun, Lunching Nguyen, Phuongmai Ahn, Bong-Hyun Leclerc, Jaime Deng, Chu-Xia Spitz, Douglas R. Gius, David Int J Biol Sci Research Paper Cellular longevity is a complex process relevant to age-related diseases including but not limited to chronic illness such as diabetes and metabolic syndromes. Two gene families have been shown to play a role in the genetic regulation of longevity; the Sirtuin and FOXO families. It is also established that nuclear Sirtuins interact with and under specific cellular conditions regulate the activity of FOXO gene family proteins. Thus, we hypothesize that a mitochondrial Sirtuin (SIRT3) might also interact with and regulate the activity of the FOXO proteins. To address this we used HCT116 cells overexpressing either wild-type or a catalytically inactive dominant negative SIRT3. For the first time we establish that FOXO3a is also a mitochondrial protein and forms a physical interaction with SIRT3 in mitochondria. Overexpression of a wild-type SIRT3 gene increase FOXO3a DNA-binding activity as well as FOXO3a dependent gene expression. Biochemical analysis of HCT116 cells over expressing the deacetylation mutant, as compared to wild-type SIRT3 gene, demonstrated an overall oxidized intracellular environment, as monitored by increase in intracellular superoxide and oxidized glutathione levels. As such, we propose that SIRT3 and FOXO3a comprise a potential mitochondrial signaling cascade response pathway. Ivyspring International Publisher 2008-09-05 /pmc/articles/PMC2532794/ /pubmed/18781224 Text en © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. |
spellingShingle | Research Paper Jacobs, Kristi Muldoon Pennington, J. Daniel Bisht, Kheem S. Aykin-Burns, Nukhet Kim, Hyun-Seok Mishra, Mark Sun, Lunching Nguyen, Phuongmai Ahn, Bong-Hyun Leclerc, Jaime Deng, Chu-Xia Spitz, Douglas R. Gius, David SIRT3 interacts with the daf-16 homolog FOXO3a in the Mitochondria, as well as increases FOXO3a Dependent Gene expression |
title | SIRT3 interacts with the daf-16 homolog FOXO3a in the Mitochondria, as well as increases FOXO3a Dependent Gene expression |
title_full | SIRT3 interacts with the daf-16 homolog FOXO3a in the Mitochondria, as well as increases FOXO3a Dependent Gene expression |
title_fullStr | SIRT3 interacts with the daf-16 homolog FOXO3a in the Mitochondria, as well as increases FOXO3a Dependent Gene expression |
title_full_unstemmed | SIRT3 interacts with the daf-16 homolog FOXO3a in the Mitochondria, as well as increases FOXO3a Dependent Gene expression |
title_short | SIRT3 interacts with the daf-16 homolog FOXO3a in the Mitochondria, as well as increases FOXO3a Dependent Gene expression |
title_sort | sirt3 interacts with the daf-16 homolog foxo3a in the mitochondria, as well as increases foxo3a dependent gene expression |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2532794/ https://www.ncbi.nlm.nih.gov/pubmed/18781224 |
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