Spontaneous and evoked neuronal activities regulate movements of single neuronal mitochondria.
Mitochondria produce ATP and act as internal Ca2+ storage sites in neurons. Their localization at active synapses can be beneficial both for the maintenance of normal neuronal activity and for preventing neurodegeneration. Mitochondrial distribution in neurons is a dynamic process that can, in turn, be determined by their activity. To examine these relationships, we used respiratory neurons that possess persistent rhythmic activity, to which mitochondria substantially contributed. Mitochondria were visualized using potentiometric dyes and two-photon microscopy. The trajectories of mitochondrial movements were obtained by single particle tracking. Spontaneous and evoked synaptic activity and intracellular Ca2+ were measured by using FM 1-43 and fura-2, respectively. Inhibition of synaptic activity with N-type Ca2+ and Na+ channel blockers, omega-conotoxin GVIA, and tetrodotoxin, increased the run-lengths of the directed transport. After brief periods of spontaneous synaptic activity and after membrane depolarization, mitochondrial movements were inhibited in correlation with the duration of intracellular [Ca2+] elevations. Movements of mitochondria were also suppressed after membrane depolarization in Ca2+-free solutions, indicating that the effects of Ca2+ are indirect and other factors, e.g., ATP depletion, may be involved. Through the use of experimentally determined parameters of mitochondrial motions, we modeled the behavior of mitochondrial ensembles and showed a tendency of mitochondria to produce linear aggregates whose formation is enhanced by irregularities of mitochondrial movements. We propose that accumulation and clustering of mitochondria in neurons are caused by interruptions in the directed transport of mitochondria, leading to the inhibition of their movements at the active synapses.
DFG-Center of Molecular Physiology of the Brain, Department of Neuro- and Sensory Physiology, Georg-August-University, Göttingen, Humboldtallee 23, 37073, Germany. smirono@gwdg.de
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D000818:Animals; D000831:Animals, Newborn; D020013:Calcium Signaling / Q000502:physiology; D005071:Evoked Potentials / Q000502:physiology*; D005260:Female; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*