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bioRxiv · 10.1101/216093

Mitochondrial Ultrastructure Is Coupled to Synaptic Performance at Axonal Release Sites

Cserep, C.·Posfai, B.·Schwarcz, A. D.·Denes, A.
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Abstract

VISUAL ABSTRACT O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY\n\nSIGNIFICANCE STATEMENTNeuronal networks are highly dynamic structures: cellular morphology and synaptic strength is changing as information is processed and stored. This means that the demand for mitochondrial supply is changing in space and time in neurons. Since the architecture ultimately determines the output performance of these organelles, we hypothesized that the ultrastructure of axonal mitochondria could well be a major parameter of adjusting their performance to the actual energetic needs of the synapse. Our results - describing a cell-type independent and synapse-specific correlation between mitochondrial ultrastructure, mitochondrial molecular fingerprints and synaptic performance - highlight the importance of activity-dependent ultrastructural plasticity of these organelles in neurons, and suggest an even more prominent role for mitochondria in neuroplasticity, than it was thought previously.\n\nABSTRACTMitochondrial function in neurons is tightly linked with metabolic and signalling mechanisms that ultimately determine neuronal performance. The subcellular distribution of these organelles is dynamically regulated as they are directed to axonal release sites on demand, but whether mitochondrial internal ultrastructure and molecular properties would reflect the actual performance requirements in a synapse-specific manner, remains to be established. Here, we examined performance-determining ultrastructural features of presynaptic mitochondria in GABAergic and glutamatergic axons of mice and human. Using electron-tomography and super-resolution microscopy we found, that these features were coupled to synaptic strength: mitochondria in boutons with high synaptic activity exhibited an ultrastructure optimized for high rate metabolism and contained higher levels of the respiratory chain protein cytochrome-c than mitochondria in boutons with lower activity. The strong, cell-type independent correlation between mitochondrial ultrastructure, molecular fingerprints and synaptic performance suggests that changes in synaptic activity could trigger ultrastructural plasticity of presynaptic mitochondria, likely to adjust their performance to the actual metabolic demand.

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Cserep, C., Posfai, B., Schwarcz, A. D., Denes, A.. 2017-11-08. Mitochondrial Ultrastructure Is Coupled to Synaptic Performance at Axonal Release Sites. https://doi.org/10.1101/216093

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