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Mitochondrial protein biogenesis in the synapse is supported by local translation
Author(s) -
Kuzniewska Bozena,
Cysewski Dominik,
Wasilewski Michal,
Sakowska Paulina,
Milek Jacek,
Kulinski Tomasz M,
Winiarski Maciej,
Kozielewicz Pawel,
Knapska Ewelina,
Dadlez Michal,
Chacinska Agnieszka,
Dziembowski Andrzej,
Dziembowska Magdalena
Publication year - 2020
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201948882
Subject(s) - mitochondrial biogenesis , biogenesis , library science , biology , mitochondrion , microbiology and biotechnology , genetics , computer science , gene
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.