Mitochondrial protein biogenesis in the synapse is supported by local translation
| Autor: | Tomasz M. Kulinski, Jacek Milek, Michał Wasilewski, Bozena Kuzniewska, Ewelina Knapska, Agnieszka Chacinska, Maciej Winiarski, Michal Dadlez, Paulina Sakowska, Magdalena Dziembowska, Paweł Kozielewicz, And Andrzej Dziembowski, Dominik Cysewski |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Proteomics
Dendritic spine Respiratory chain translation Mitochondrion Biochemistry Synapse Mitochondrial Proteins 03 medical and health sciences Fragile X Mental Retardation Protein Mice 0302 clinical medicine Report Genetics medicine Animals Molecular Biology 030304 developmental biology Mice Knockout 0303 health sciences Chemistry Translation (biology) Protein Biosynthesis & Quality Control FMR1 Cell biology mitochondria medicine.anatomical_structure Fragile X Syndrome Synapses Neuron 030217 neurology & neurosurgery Biogenesis Reports Neuroscience |
| Zdroj: | EMBO Reports |
| ISSN: | 1469-3178 1469-221X |
| Popis: | Synapses are the regions of the neuron that enable the transmission and propagation of action potentials on the cost of high energy consumption and elevated demand for mitochondrial ATP production. The rapid changes in local energetic requirements at dendritic spines imply the role of mitochondria in the maintenance of their homeostasis. Using global proteomic analysis supported with complementary experimental approaches, we show that an essential pool of mitochondrial proteins is locally produced at the synapse indicating that mitochondrial protein biogenesis takes place locally to maintain functional mitochondria in axons and dendrites. Furthermore, we show that stimulation of synaptoneurosomes induces the local synthesis of mitochondrial proteins that are transported to the mitochondria and incorporated into the protein supercomplexes of the respiratory chain. Importantly, in a mouse model of fragile X syndrome, Fmr1 KO mice, a common disease associated with dysregulation of synaptic protein synthesis, we observed altered morphology and respiration rates of synaptic mitochondria. That indicates that the local production of mitochondrial proteins plays an essential role in synaptic functions. Using global proteomic analysis and a mouse model of fragile X syndrome, Fmr1 KO mice, this study reveals that the local production of mitochondrial proteins plays an essential role in synaptic functions. |
| Databáze: | OpenAIRE |
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