Presynaptic Mitochondrial Volume and Packing Density Scale with Presynaptic Power Demand

Area of Science:

• Neuroscience
• Cellular Biology
• Bioenergetics

Background:

• Stable neural function necessitates energy supply matching neuronal activity demands.
• The relationship between presynaptic power needs and bioenergetic machinery volume remains unquantified.
• Understanding neuronal energy metabolism is crucial for comprehending neural processing limitations.

Purpose of the Study:

• To quantify the power demands of motor nerve terminals in *Drosophila* larvae.
• To investigate the relationship between presynaptic power demands and the volume of bioenergetic machinery (mitochondria and cytosol).
• To estimate ATP production rates from glycolysis and oxidative phosphorylation in presynaptic terminals.

Main Methods:

• Direct measurement of neurotransmitter release and Ca2+ entry in *Drosophila* motor nerve terminals.
• Theoretical estimation of Na+ entry and resting power demands.
• Electron microscopy to determine mitochondrial volume and density.

Main Results:

• Terminals with higher power demands exhibited greater mitochondrial volume, indicating allocation based on energy needs.
• High power demand-to-volume ratio terminals possessed larger, denser mitochondria.
• Estimated ATP production rates: mitochondria supply 52–963 nmol·min−1·µl−1, glycolysis 0.24–4.36 nmol·min−1·µl−1 at rest and during activity, respectively.

Conclusions:

• Presynaptic terminals optimize mitochondrial volume and density to meet power demands over time.
• Oxidative phosphorylation plays a primary role in presynaptic energy production.
• Provides the first in vivo estimates of energy production rates per unit volume of presynaptic mitochondria and cytosol.