Stress-induced dynamic regulation of mitochondrial STAT3 and its association with cyclophilin D reduces mitochondrial ROS production
Signal Transducer and Activator of Transcription 3 (STAT3) has been tied to various physiological and pathological functions, mainly as a transcription factor that translocates to the nucleus upon tyrosine phosphorylation induced by cytokine stimulation. In addition, a small pool of STAT3 resides in...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
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American Association for the Advancement of Science
2017
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| Online Access: | https://eprints.nottingham.ac.uk/41774/ |
| _version_ | 1848796351374032896 |
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| author | Meier, Jeremy A. Hyun, Moonjung Cantwell, Marc Raza, Ali Mertens, Claudia Raje, Vidisha Sisler, Jennifer Tracy, Erin Torres-Odio, Sylvia Gispert, Suzana Shaw, Peter E. Baumann, Heinz Bandyopadhyay, Dipankar Takabe, Kazuaki Larner, Andrew C. |
| author_facet | Meier, Jeremy A. Hyun, Moonjung Cantwell, Marc Raza, Ali Mertens, Claudia Raje, Vidisha Sisler, Jennifer Tracy, Erin Torres-Odio, Sylvia Gispert, Suzana Shaw, Peter E. Baumann, Heinz Bandyopadhyay, Dipankar Takabe, Kazuaki Larner, Andrew C. |
| author_sort | Meier, Jeremy A. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Signal Transducer and Activator of Transcription 3 (STAT3) has been tied to various physiological and pathological functions, mainly as a transcription factor that translocates to the nucleus upon tyrosine phosphorylation induced by cytokine stimulation. In addition, a small pool of STAT3 resides in the mitochondria where it serves as a sensor for various metabolic stressors including reactive oxygen species (ROS). Mitochondrially-localized STAT3 largely exerts its effects through direct or indirect regulation of the activity of the electron transport chain (ETC). It has been assumed that STAT3 amounts in the mitochondria are static. We showed that various stimuli, including oxidative stress and cytokines, triggered a signaling cascade that resulted in a rapid loss of mitochondrially-localized STAT3. Recovery of the mitochondrial pool of STAT3 over time depended upon phosphorylation of Ser727 in STAT3 and new protein synthesis. Under these conditions, mitochondrially-localized STAT3 also became competent to bind to cyclophilin D (CypD). Binding of STAT3 to CypD was mediated by the N-terminus of STAT3, which was also important for reducing mitochondrial ROS production after oxidative stress. These results outline a role for mitochondrially-localized STAT3 in sensing and responding to external stimuli. |
| first_indexed | 2025-11-14T19:46:36Z |
| format | Article |
| id | nottingham-41774 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:46:36Z |
| publishDate | 2017 |
| publisher | American Association for the Advancement of Science |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-417742020-05-04T18:39:26Z https://eprints.nottingham.ac.uk/41774/ Stress-induced dynamic regulation of mitochondrial STAT3 and its association with cyclophilin D reduces mitochondrial ROS production Meier, Jeremy A. Hyun, Moonjung Cantwell, Marc Raza, Ali Mertens, Claudia Raje, Vidisha Sisler, Jennifer Tracy, Erin Torres-Odio, Sylvia Gispert, Suzana Shaw, Peter E. Baumann, Heinz Bandyopadhyay, Dipankar Takabe, Kazuaki Larner, Andrew C. Signal Transducer and Activator of Transcription 3 (STAT3) has been tied to various physiological and pathological functions, mainly as a transcription factor that translocates to the nucleus upon tyrosine phosphorylation induced by cytokine stimulation. In addition, a small pool of STAT3 resides in the mitochondria where it serves as a sensor for various metabolic stressors including reactive oxygen species (ROS). Mitochondrially-localized STAT3 largely exerts its effects through direct or indirect regulation of the activity of the electron transport chain (ETC). It has been assumed that STAT3 amounts in the mitochondria are static. We showed that various stimuli, including oxidative stress and cytokines, triggered a signaling cascade that resulted in a rapid loss of mitochondrially-localized STAT3. Recovery of the mitochondrial pool of STAT3 over time depended upon phosphorylation of Ser727 in STAT3 and new protein synthesis. Under these conditions, mitochondrially-localized STAT3 also became competent to bind to cyclophilin D (CypD). Binding of STAT3 to CypD was mediated by the N-terminus of STAT3, which was also important for reducing mitochondrial ROS production after oxidative stress. These results outline a role for mitochondrially-localized STAT3 in sensing and responding to external stimuli. American Association for the Advancement of Science 2017-03-28 Article PeerReviewed Meier, Jeremy A., Hyun, Moonjung, Cantwell, Marc, Raza, Ali, Mertens, Claudia, Raje, Vidisha, Sisler, Jennifer, Tracy, Erin, Torres-Odio, Sylvia, Gispert, Suzana, Shaw, Peter E., Baumann, Heinz, Bandyopadhyay, Dipankar, Takabe, Kazuaki and Larner, Andrew C. (2017) Stress-induced dynamic regulation of mitochondrial STAT3 and its association with cyclophilin D reduces mitochondrial ROS production. Science Signaling, 10 (472). eaag2588. ISSN 1937-9145 http://stke.sciencemag.org/content/10/472/eaag2588.long doi:10.1126/scisignal.aag2588 doi:10.1126/scisignal.aag2588 |
| spellingShingle | Meier, Jeremy A. Hyun, Moonjung Cantwell, Marc Raza, Ali Mertens, Claudia Raje, Vidisha Sisler, Jennifer Tracy, Erin Torres-Odio, Sylvia Gispert, Suzana Shaw, Peter E. Baumann, Heinz Bandyopadhyay, Dipankar Takabe, Kazuaki Larner, Andrew C. Stress-induced dynamic regulation of mitochondrial STAT3 and its association with cyclophilin D reduces mitochondrial ROS production |
| title | Stress-induced dynamic regulation of mitochondrial STAT3 and its association with cyclophilin D reduces mitochondrial ROS production |
| title_full | Stress-induced dynamic regulation of mitochondrial STAT3 and its association with cyclophilin D reduces mitochondrial ROS production |
| title_fullStr | Stress-induced dynamic regulation of mitochondrial STAT3 and its association with cyclophilin D reduces mitochondrial ROS production |
| title_full_unstemmed | Stress-induced dynamic regulation of mitochondrial STAT3 and its association with cyclophilin D reduces mitochondrial ROS production |
| title_short | Stress-induced dynamic regulation of mitochondrial STAT3 and its association with cyclophilin D reduces mitochondrial ROS production |
| title_sort | stress-induced dynamic regulation of mitochondrial stat3 and its association with cyclophilin d reduces mitochondrial ros production |
| url | https://eprints.nottingham.ac.uk/41774/ https://eprints.nottingham.ac.uk/41774/ https://eprints.nottingham.ac.uk/41774/ |