Ndufs4 ablation decreases synaptophysin expression in hippocampus

• Published in: Scientific reports Vol. 11; no. 1; p. 10969
• Main Authors: Shil, Subrata Kumar, Kagawa, Yoshiteru, Umaru, Banlanjo Abdulaziz, Nanto-Hara, Fumika, Miyazaki, Hirofumi, Yamamoto, Yui, Kobayashi, Shuhei, Suzuki, Chitose, Abe, Takaaki, Owada, Yuji
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26-05-2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/337; 631/378; Ablation; Adenosine Triphosphate - biosynthesis; Alzheimer's disease; Animals; Astrocytes; Astrocytes - metabolism; Brain; Cells, Cultured; Cerebral Cortex - metabolism; Convulsions & seizures; Dehydrogenases; Electron transport chain; Electron Transport Complex I - deficiency; Electron Transport Complex I - genetics; Electron Transport Complex I - metabolism; Electron Transport Complex I - physiology; Enzymes; Extracellular signal-regulated kinase; Glial fibrillary acidic protein; Hippocampus; Hippocampus - metabolism; Humanities and Social Sciences; Iron-sulfur proteins; Kinases; Localization; Male; Mice; Mice, Knockout; Mitochondria; Mitochondria - metabolism; multidisciplinary; Mutation; NADH; NADH dehydrogenase; NADH dehydrogenase (ubiquinone); NADH-ubiquinone oxidoreductase; Nerve Tissue Proteins - deficiency; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - physiology; Neural plasticity; Neurites - ultrastructure; Neurodegenerative diseases; Neurons; Neurons - metabolism; Neurons - ultrastructure; Organ Specificity; Parkinson's disease; Proteins; Respiration; Science; Science (multidisciplinary); Signal transduction; Synaptophysin; Synaptophysin - biosynthesis; Synaptophysin - genetics; Ubiquinone
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-90127-4

Altered function of mitochondrial respiratory chain in brain cells is related to many neurodegenerative diseases. NADH Dehydrogenase (Ubiquinone) Fe-S protein 4 (Ndufs4) is one of the subunits of mitochondrial complex I and its mutation in human is associated with Leigh syndrome. However, the molecular biological role of Ndufs4 in neuronal function is poorly understood. In this study, upon Ndufs4 expression confirmation in NeuN-positive neurons, and GFAP-positive astrocytes in WT mouse hippocampus, we found significant decrease of mitochondrial respiration in Ndufs4-KO mouse hippocampus. Although there was no change in the number of NeuN positive neurons in Ndufs4-KO hippocampus, the expression of synaptophysin, a presynaptic protein, was significantly decreased. To investigate the detailed mechanism, we silenced Ndufs4 in Neuro-2a cells and we observed shorter neurite lengths with decreased expression of synaptophysin. Furthermore, western blot analysis for phosphorylated extracellular regulated kinase (pERK) revealed that Ndufs4 silencing decreases the activity of ERK signalling. These results suggest that Ndufs4-modulated mitochondrial activity may be involved in neuroplasticity via regulating synaptophysin expression.