SIRT3 interacts with the daf-16 homolog FOXO3a in the Mitochondria, as well as increases FOXO3a Dependent Gene expression
<p>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...
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| Format: | Article |
| Language: | English |
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Ivyspring International Publisher
2008-01-01
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| Series: | International Journal of Biological Sciences |
| Online Access: | http://www.biolsci.org/v04p0291.htm |
| _version_ | 1817976567110828032 |
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| author | Kristi Muldoon Jacobs, J. Daniel Pennington, Kheem S. Bisht, Nukhet Aykin-Burns, Hyun-Seok Kim, Mark Mishra, Lunching Sun, Phuongmai Nguyen, Bong-Hyun Ahn, Jaime Leclerc, Chu-Xia Deng, Douglas R. Spitz, David Gius |
| author_facet | Kristi Muldoon Jacobs, J. Daniel Pennington, Kheem S. Bisht, Nukhet Aykin-Burns, Hyun-Seok Kim, Mark Mishra, Lunching Sun, Phuongmai Nguyen, Bong-Hyun Ahn, Jaime Leclerc, Chu-Xia Deng, Douglas R. Spitz, David Gius |
| author_sort | Kristi Muldoon Jacobs, J. Daniel Pennington, Kheem S. Bisht, Nukhet Aykin-Burns, Hyun-Seok Kim, Mark Mishra, Lunching Sun, Phuongmai Nguyen, Bong-Hyun Ahn, Jaime Leclerc, Chu-Xia Deng, Douglas R. Spitz, David Gius |
| collection | DOAJ |
| description | <p>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 (<i>SIRT3</i>) 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 <i>SIRT3</i>. 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 <i>SIRT3</i> 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 <i>SIRT3</i> gene, demonstrated an overall oxidized intracellular environment, as monitored by increase in intracellular superoxide and oxidized glutathione levels. As such, we propose that <i>SIRT3</i> and FOXO3a comprise a potential mitochondrial signaling cascade response pathway.</p> |
| first_indexed | 2024-04-13T22:05:15Z |
| format | Article |
| id | doaj.art-7a77212e33ef4528a0d7f6334e6ca910 |
| institution | Directory Open Access Journal |
| issn | 1449-2288 |
| language | English |
| last_indexed | 2024-04-13T22:05:15Z |
| publishDate | 2008-01-01 |
| publisher | Ivyspring International Publisher |
| record_format | Article |
| series | International Journal of Biological Sciences |
| spelling | doaj.art-7a77212e33ef4528a0d7f6334e6ca9102022-12-22T02:27:59ZengIvyspring International PublisherInternational Journal of Biological Sciences1449-22882008-01-0145291299SIRT3 interacts with the daf-16 homolog FOXO3a in the Mitochondria, as well as increases FOXO3a Dependent Gene expressionKristi Muldoon Jacobs, J. Daniel Pennington, Kheem S. Bisht, Nukhet Aykin-Burns, Hyun-Seok Kim, Mark Mishra, Lunching Sun, Phuongmai Nguyen, Bong-Hyun Ahn, Jaime Leclerc, Chu-Xia Deng, Douglas R. Spitz, David Gius<p>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 (<i>SIRT3</i>) 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 <i>SIRT3</i>. 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 <i>SIRT3</i> 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 <i>SIRT3</i> gene, demonstrated an overall oxidized intracellular environment, as monitored by increase in intracellular superoxide and oxidized glutathione levels. As such, we propose that <i>SIRT3</i> and FOXO3a comprise a potential mitochondrial signaling cascade response pathway.</p>http://www.biolsci.org/v04p0291.htm |
| spellingShingle | Kristi Muldoon Jacobs, J. Daniel Pennington, Kheem S. Bisht, Nukhet Aykin-Burns, Hyun-Seok Kim, Mark Mishra, Lunching Sun, Phuongmai Nguyen, Bong-Hyun Ahn, Jaime Leclerc, Chu-Xia Deng, Douglas R. Spitz, David Gius SIRT3 interacts with the daf-16 homolog FOXO3a in the Mitochondria, as well as increases FOXO3a Dependent Gene expression International Journal of Biological Sciences |
| 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 |
| url | http://www.biolsci.org/v04p0291.htm |
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