Please use this identifier to cite or link to this item: https://doi.org/10.1242/jcs.01130
Title: Axonal mitochondrial transport and potential are correlated
Authors: Miller, K.E
Sheetz, M.P 
Keywords: adenosine triphosphate
citrinin
deoxyglucose
mannitol
animal cell
article
controlled study
correlation coefficient
electron transport
growth cone
histochemistry
micropipette
mitochondrial energy transfer
mitochondrial membrane
mitochondrial respiration
nerve cell membrane potential
nerve fiber transport
nonhuman
priority journal
regulatory mechanism
statistical analysis
Adenosine Triphosphate
Animals
Antimycin A
Axons
Benzimidazoles
Biological Transport
Carbocyanines
Carbonyl Cyanide m-Chlorophenyl Hydrazone
Cells, Cultured
Chick Embryo
Deoxyglucose
Electron Transport Complex III
Fluorescent Dyes
Ganglia, Spinal
Growth Cones
Mannitol
Membrane Potentials
Mitochondria
Neurons
Statistics
Uncoupling Agents
Animalia
Issue Date: 2004
Citation: Miller, K.E, Sheetz, M.P (2004). Axonal mitochondrial transport and potential are correlated. Journal of Cell Science 117 (13) : 2791-2804. ScholarBank@NUS Repository. https://doi.org/10.1242/jcs.01130
Rights: Attribution 4.0 International
Abstract: Disruption of axonal transport leads to a disorganized distribution of mitochondria and other organelles and is thought to be responsible for some types of neuronal disease. The reason for bidirectional transport of mitochondria is unknown. We have developed and applied a set of statistical methods and found that axonal mitochondria are uniformly distributed. Analysis of fast axonal transport showed that the uniform distribution arose from the clustering of the stopping events of fast axonal transport in the middle of the gaps between stationary mitochondria. To test whether transport was correlated with ATP production, we added metabolic inhibitors locally by micropipette. Whereas applying CCCP (a mitochondrial uncoupler) blocked mitochondrial transport, as has been previously reported, treatment with antimycin (an inhibitor of electron transport at complex III) caused increases in retrograde mitochondrial transport. Application of 2-deoxyglucose did not decrease transport compared with the mannitol control. To determine whether mitochondrial transport was correlated with mitochondrial potential, we stained the neurons with the mitochondrial potential-sensing dye JC-1. We found that ?90% of mitochondria with high potential were transported towards the growth cone and ?80% of mitochondria with low potential were transported towards the cell body. These experiments show for the first time that a uniform mitochondrial distribution is generated by local regulation of the stopping events of fast mitochondrial transport, and that the direction of mitochondrial transport is correlated with mitochondrial potential. These results have implications for axonal clogging, autophagy, apoptosis and Alzheimer's disease.
Source Title: Journal of Cell Science
URI: https://scholarbank.nus.edu.sg/handle/10635/181106
ISSN: 00219533
DOI: 10.1242/jcs.01130
Rights: Attribution 4.0 International
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