Redox signaling modulates axonal microtubule organization and induces a specific phosphorylation signature of microtubule-regulating proteins
Many life processes are regulated by physiological redox signaling, but excessive oxidative stress can damage biomolecules and contribute to disease. Neuronal microtubules are critically involved in axon homeostasis, regulation of axonal transport, and neurodegenerative processes. However, whether a...
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Elsevier
2025-06-01
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| Series: | Redox Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231725001399 |
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| author | Christian Conze Nataliya I. Trushina Nanci Monteiro-Abreu Lisha Singh Daniel Villar Romero Eike Wienbeuker Anna-Sophie Schwarze Michael Holtmannspötter Lidia Bakota Roland Brandt |
| author_facet | Christian Conze Nataliya I. Trushina Nanci Monteiro-Abreu Lisha Singh Daniel Villar Romero Eike Wienbeuker Anna-Sophie Schwarze Michael Holtmannspötter Lidia Bakota Roland Brandt |
| author_sort | Christian Conze |
| collection | DOAJ |
| description | Many life processes are regulated by physiological redox signaling, but excessive oxidative stress can damage biomolecules and contribute to disease. Neuronal microtubules are critically involved in axon homeostasis, regulation of axonal transport, and neurodegenerative processes. However, whether and how physiological redox signaling affects axonal microtubules is largely unknown. Using live cell imaging and super-resolution microscopy, we show that subtoxic concentrations of the central redox metabolite hydrogen peroxide increase axonal microtubule dynamics, alter the structure of the axonal microtubule array, and affect the efficiency of axonal transport. We report that the mitochondria-targeting antioxidant SkQ1 and the microtubule stabilizer EpoD abolish the increase in microtubule dynamics. We found that hydrogen peroxide specifically modulates the phosphorylation state of microtubule-regulating proteins, which differs from arsenite as an alternative stress inducer, and induces a largely non-overlapping phosphorylation pattern of MAP1B as a main target. Cell-wide phosphoproteome analysis revealed signaling pathways that are inversely activated by hydrogen peroxide and arsenite. In particular, hydrogen peroxide treatment was associated with kinases that suppress apoptosis and regulate brain metabolism (PRKDC, CK2, PDKs), suggesting that these pathways play a central role in physiological redox signaling and modulation of axonal microtubule organization. The results suggest that the redox metabolite and second messenger hydrogen peroxide induces rapid and local reorganization of the microtubule array in response to mitochondrial activity or as a messenger from neighboring cells by activating specific signaling cascades. |
| format | Article |
| id | doaj-art-161a2a64c259444f930fca5e86869333 |
| institution | OA Journals |
| issn | 2213-2317 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj-art-161a2a64c259444f930fca5e868693332025-08-20T02:31:56ZengElsevierRedox Biology2213-23172025-06-018310362610.1016/j.redox.2025.103626Redox signaling modulates axonal microtubule organization and induces a specific phosphorylation signature of microtubule-regulating proteinsChristian Conze0Nataliya I. Trushina1Nanci Monteiro-Abreu2Lisha Singh3Daniel Villar Romero4Eike Wienbeuker5Anna-Sophie Schwarze6Michael Holtmannspötter7Lidia Bakota8Roland Brandt9Department of Neurobiology, School of Biology/Chemistry, Osnabrück University, GermanyDepartment of Neurobiology, School of Biology/Chemistry, Osnabrück University, GermanyDepartment of Neurobiology, School of Biology/Chemistry, Osnabrück University, GermanyDepartment of Neurobiology, School of Biology/Chemistry, Osnabrück University, GermanyDepartment of Neurobiology, School of Biology/Chemistry, Osnabrück University, GermanyDepartment of Neurobiology, School of Biology/Chemistry, Osnabrück University, GermanyDepartment of Neurobiology, School of Biology/Chemistry, Osnabrück University, GermanyCenter for Cellular Nanoanalytics, Osnabrück University, GermanyDepartment of Neurobiology, School of Biology/Chemistry, Osnabrück University, GermanyDepartment of Neurobiology, School of Biology/Chemistry, Osnabrück University, Germany; Center for Cellular Nanoanalytics, Osnabrück University, Germany; Institute of Cognitive Science, Osnabrück University, Germany; Corresponding author. Department of Neurobiology, School of Biology/Chemistry, Osnabrück University, Germany.Many life processes are regulated by physiological redox signaling, but excessive oxidative stress can damage biomolecules and contribute to disease. Neuronal microtubules are critically involved in axon homeostasis, regulation of axonal transport, and neurodegenerative processes. However, whether and how physiological redox signaling affects axonal microtubules is largely unknown. Using live cell imaging and super-resolution microscopy, we show that subtoxic concentrations of the central redox metabolite hydrogen peroxide increase axonal microtubule dynamics, alter the structure of the axonal microtubule array, and affect the efficiency of axonal transport. We report that the mitochondria-targeting antioxidant SkQ1 and the microtubule stabilizer EpoD abolish the increase in microtubule dynamics. We found that hydrogen peroxide specifically modulates the phosphorylation state of microtubule-regulating proteins, which differs from arsenite as an alternative stress inducer, and induces a largely non-overlapping phosphorylation pattern of MAP1B as a main target. Cell-wide phosphoproteome analysis revealed signaling pathways that are inversely activated by hydrogen peroxide and arsenite. In particular, hydrogen peroxide treatment was associated with kinases that suppress apoptosis and regulate brain metabolism (PRKDC, CK2, PDKs), suggesting that these pathways play a central role in physiological redox signaling and modulation of axonal microtubule organization. The results suggest that the redox metabolite and second messenger hydrogen peroxide induces rapid and local reorganization of the microtubule array in response to mitochondrial activity or as a messenger from neighboring cells by activating specific signaling cascades.http://www.sciencedirect.com/science/article/pii/S2213231725001399MicrotubulesTauAxonRedox signallingHydrogen peroxide |
| spellingShingle | Christian Conze Nataliya I. Trushina Nanci Monteiro-Abreu Lisha Singh Daniel Villar Romero Eike Wienbeuker Anna-Sophie Schwarze Michael Holtmannspötter Lidia Bakota Roland Brandt Redox signaling modulates axonal microtubule organization and induces a specific phosphorylation signature of microtubule-regulating proteins Redox Biology Microtubules Tau Axon Redox signalling Hydrogen peroxide |
| title | Redox signaling modulates axonal microtubule organization and induces a specific phosphorylation signature of microtubule-regulating proteins |
| title_full | Redox signaling modulates axonal microtubule organization and induces a specific phosphorylation signature of microtubule-regulating proteins |
| title_fullStr | Redox signaling modulates axonal microtubule organization and induces a specific phosphorylation signature of microtubule-regulating proteins |
| title_full_unstemmed | Redox signaling modulates axonal microtubule organization and induces a specific phosphorylation signature of microtubule-regulating proteins |
| title_short | Redox signaling modulates axonal microtubule organization and induces a specific phosphorylation signature of microtubule-regulating proteins |
| title_sort | redox signaling modulates axonal microtubule organization and induces a specific phosphorylation signature of microtubule regulating proteins |
| topic | Microtubules Tau Axon Redox signalling Hydrogen peroxide |
| url | http://www.sciencedirect.com/science/article/pii/S2213231725001399 |
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