Mitochondrial Superoxide Dismutase Specifies Early Neural Commitment by Modulating Mitochondrial Dynamics
Summary: Studies revealing molecular mechanisms underlying neural specification have majorly focused on the role played by different transcription factors, but less on non-nuclear components. Earlier, we reported mitochondrial superoxide dismutase (SOD2) to be essential for self-renewal and pluripot...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-10-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004220307562 |
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| author | Smitha Bhaskar Preethi Sheshadri Joel P. Joseph Chandrakanta Potdar Jyothi Prasanna Anujith Kumar |
| author_facet | Smitha Bhaskar Preethi Sheshadri Joel P. Joseph Chandrakanta Potdar Jyothi Prasanna Anujith Kumar |
| author_sort | Smitha Bhaskar |
| collection | DOAJ |
| description | Summary: Studies revealing molecular mechanisms underlying neural specification have majorly focused on the role played by different transcription factors, but less on non-nuclear components. Earlier, we reported mitochondrial superoxide dismutase (SOD2) to be essential for self-renewal and pluripotency of mouse embryonic stem cells (mESCs). In the present study, we found SOD2 to be specifically required for neural lineage, but not the meso- or endoderm specification. Temporally, SOD2 regulated early neural genes, but not the matured genes, by modulating mitochondrial dynamics—specifically by enhancing the mitochondrial fusion protein Mitofusin 2 (MFN2). Bio-complementation strategy further confirmed SOD2 to enhance mitochondrial fusion process independent of its antioxidant activity. Over-expression of SOD2 along with OCT4, but neither alone, transdifferentiated mouse fibroblasts to neural progenitor-like colonies, conclusively proving the neurogenic potential of SOD2. In conclusion, our findings accredit a novel role for SOD2 in early neural lineage specification. |
| first_indexed | 2024-12-11T13:03:14Z |
| format | Article |
| id | doaj.art-f68df843cc594b26ad55106118bffd38 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-11T13:03:14Z |
| publishDate | 2020-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-f68df843cc594b26ad55106118bffd382022-12-22T01:06:24ZengElsevieriScience2589-00422020-10-012310101564Mitochondrial Superoxide Dismutase Specifies Early Neural Commitment by Modulating Mitochondrial DynamicsSmitha Bhaskar0Preethi Sheshadri1Joel P. Joseph2Chandrakanta Potdar3Jyothi Prasanna4Anujith Kumar5Manipal Institute of Regenerative Medicine, Manipal Academy of Higher Education, Allalasandra, Yelahanka, Bengaluru, 560065 Karnataka, IndiaManipal Institute of Regenerative Medicine, Manipal Academy of Higher Education, Allalasandra, Yelahanka, Bengaluru, 560065 Karnataka, IndiaManipal Institute of Regenerative Medicine, Manipal Academy of Higher Education, Allalasandra, Yelahanka, Bengaluru, 560065 Karnataka, IndiaManipal Institute of Regenerative Medicine, Manipal Academy of Higher Education, Allalasandra, Yelahanka, Bengaluru, 560065 Karnataka, IndiaManipal Institute of Regenerative Medicine, Manipal Academy of Higher Education, Allalasandra, Yelahanka, Bengaluru, 560065 Karnataka, IndiaManipal Institute of Regenerative Medicine, Manipal Academy of Higher Education, Allalasandra, Yelahanka, Bengaluru, 560065 Karnataka, India; Corresponding authorSummary: Studies revealing molecular mechanisms underlying neural specification have majorly focused on the role played by different transcription factors, but less on non-nuclear components. Earlier, we reported mitochondrial superoxide dismutase (SOD2) to be essential for self-renewal and pluripotency of mouse embryonic stem cells (mESCs). In the present study, we found SOD2 to be specifically required for neural lineage, but not the meso- or endoderm specification. Temporally, SOD2 regulated early neural genes, but not the matured genes, by modulating mitochondrial dynamics—specifically by enhancing the mitochondrial fusion protein Mitofusin 2 (MFN2). Bio-complementation strategy further confirmed SOD2 to enhance mitochondrial fusion process independent of its antioxidant activity. Over-expression of SOD2 along with OCT4, but neither alone, transdifferentiated mouse fibroblasts to neural progenitor-like colonies, conclusively proving the neurogenic potential of SOD2. In conclusion, our findings accredit a novel role for SOD2 in early neural lineage specification.http://www.sciencedirect.com/science/article/pii/S2589004220307562Developmental GeneticsMolecular GeneticsDevelopmental Neuroscience |
| spellingShingle | Smitha Bhaskar Preethi Sheshadri Joel P. Joseph Chandrakanta Potdar Jyothi Prasanna Anujith Kumar Mitochondrial Superoxide Dismutase Specifies Early Neural Commitment by Modulating Mitochondrial Dynamics iScience Developmental Genetics Molecular Genetics Developmental Neuroscience |
| title | Mitochondrial Superoxide Dismutase Specifies Early Neural Commitment by Modulating Mitochondrial Dynamics |
| title_full | Mitochondrial Superoxide Dismutase Specifies Early Neural Commitment by Modulating Mitochondrial Dynamics |
| title_fullStr | Mitochondrial Superoxide Dismutase Specifies Early Neural Commitment by Modulating Mitochondrial Dynamics |
| title_full_unstemmed | Mitochondrial Superoxide Dismutase Specifies Early Neural Commitment by Modulating Mitochondrial Dynamics |
| title_short | Mitochondrial Superoxide Dismutase Specifies Early Neural Commitment by Modulating Mitochondrial Dynamics |
| title_sort | mitochondrial superoxide dismutase specifies early neural commitment by modulating mitochondrial dynamics |
| topic | Developmental Genetics Molecular Genetics Developmental Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2589004220307562 |
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