ADP regulates movements of mitochondria in neurons
Sergej Mironov 1*
1 Georg-August-University
* To whom correspondence should be addressed. E-mail: smirono{at}gwdg.de.
Submitted on July 10, 2006
Revised on August 15, 2006
Accepted on 27 December 2006
 |
Abstract |
|---|
Mitochondria often reside in subcellular regions with high metabolic demands. We examined the mechanisms which can govern the relocation of mitochondria to these sites in the respiratory neurons. Mitochondria were visualized by using TMRE and their movements were analyzed by applying a single particle tracking. Intracellular ATP ([ATP]i) was assessed by imaging the luminescence of luciferase, the fluorescence of the ATP analogue, 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 [ATP]i than to [ATP]i depletions. We propose that consumption of synaptic ATP can produce local increases in [ATP]i and facilitate the targeting of mitochondria to synapses.
Key Words:
ADP, ATP, Directed transport, Hypoxia, Respiratory neurons, Single mitochondria tracking
