Mitochondrial protein biogenesis in the synapse is supported by local translation
Bożena Kuźniewska, Dominik Cysewski, M Wasilewski, Paulina Sakowska, Jacek Miłek, Tomasz M. Kuliński, M. Winiarski, Paweł Kozielewicz, Ewelina Knapska, Michał Dadlez, Agnieszka Chacińska, Andrzej Dziembowski, Magdalena Dziembowska
Abstract
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.