Mitochondrial Superoxide Dismutase Specifies Early Neural Commitment by Modulating Mitochondrial Dynamics

Smitha Bhaskar; Preethi Sheshadri; Joel P Joseph; Chandrakanta Potdar; Jyothi Prasanna; Anujith Kumar

doi:10.1016/j.isci.2020.101564

Mitochondrial Superoxide Dismutase Specifies Early Neural Commitment by Modulating Mitochondrial Dynamics

iScience. 2020 Sep 15;23(10):101564. doi: 10.1016/j.isci.2020.101564. eCollection 2020 Oct 23.

Authors

Smitha Bhaskar¹, Preethi Sheshadri¹, Joel P Joseph¹, Chandrakanta Potdar¹, Jyothi Prasanna¹, Anujith Kumar¹

Affiliation

¹ Manipal Institute of Regenerative Medicine, Manipal Academy of Higher Education, Allalasandra, Yelahanka, Bengaluru, 560065 Karnataka, India.

Abstract

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.

Keywords: Developmental Genetics; Developmental Neuroscience; Molecular Genetics.