ADP regulates movements of mitochondria in neurons.

Mitochondria often reside in subcellular regions with high metabolic demands. We examined the mechanisms that can govern the relocation of mitochondria to these sites in respiratory neurons. Mitochondria were visualized using tetramethylrhodamineethylester, and their movements were analyzed by applying single-particle tracking. Intracellular ATP ([ATP](i)) was assessed by imaging the luminescence of luciferase, the fluorescence of the ATP analog TNP-ATP, and by monitoring the activity of K(ATP) channels. Directed movements of mitochondria were accompanied by transient increases in TNP-ATP fluorescence. Application of glutamate and hypoxia reversibly decreased [ATP](i) levels and inhibited the directed transport. Injections of ATP did not rescue the motility of mitochondria after its inhibition by hypoxia. Introduction of ADP suppressed mitochondrial movements and occluded the effects of subsequent hypoxia. Mitochondria decreased their velocity in the proximity of synapses that correlated with local [ATP](i) depletions. Using a model of motor-assisted transport and Monte Carlo simulations, we showed that mitochondrial traffic is more sensitive to increases in [ADP](i) than to [ATP](i) depletions. We propose that consumption of synaptic ATP can produce local increases in [ADP](i) and facilitate the targeting of mitochondria to synapses.

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