Systemic phospho-defective and phospho-mimetic Drp1 mice exhibit normal growth and development with altered anxiety-like behavior

• Published in: iScience Vol. 27; no. 6; p. 109874
• Main Authors: Ikeda, Arisa, Iijima, Miho, Sesaki, Hiromi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.06.2024; Elsevier
• Subjects: Behavioral neuroscience; Biochemistry; Developmental neuroscience; Molecular biology; Molecular neuroscience; Neuroscience; Molecular neuroscience; Neuroscience; Developmental neuroscience; Biochemistry; Molecular biology; Behavioral neuroscience
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2024.109874

Mitochondrial division controls the size, distribution, and turnover of this essential organelle. A dynamin-related GTPase, Drp1, drives membrane division as a force-generating mechano-chemical enzyme. Drp1 is regulated by multiple mechanisms, including phosphorylation at two primary sites: serine 579 and serine 600. While previous studies in cell culture systems have shown that Drp1 S579 phosphorylation promotes mitochondrial division, its physiological functions remained unclear. Here, we generated phospho-mimetic Drp1 S579D and phospho-defective Drp1 S579R mice using the CRISPR-Cas system. Both mouse models exhibited normal growth, development, and breeding. We found that Drp1 is highly phosphorylated at S579 in brain neurons. Notably, the Drp1 S579D mice showed decreased anxiety-like behaviors, whereas the Drp1 S579R mice displayed increased anxiety-like behaviors. These findings suggest a critical role for Drp1 S579 phosphorylation in brain function. The Drp1 S579D and S579R mice thus offer valuable in vivo models for specific analysis of Drp1 S579 phosphorylation. [Display omitted] •Drp1 is highly phosphorylated at S579 in post-mitotic neurons in mice•Drp1 S579 phosphorylation is dispensable for development and growth in mice•Drp1 S579 phosphorylation influences anxiety behaviors•Drp1 phospho-deficient and phospho-mimetic mice provide useful animal models Biochemistry; Molecular biology; Neuroscience; Behavioral neuroscience; Molecular neuroscience; Developmental neuroscience