Creatine kinase B deficient neurons exhibit an increased fraction of motile mitochondria.
Neurons require an elaborate system of intracellular transport to distribute cargo throughout axonal and dendritic projections. Active anterograde and retrograde transport of mitochondria serve in local energy distribution, but at the same time also require input of ATP.
Here we studied whether brain-type creatine kinase (CK-B), a key enzyme for high-energy phosphoryl transfer between ATP and CrP in brain, has an intermediary role in the reciprocal coordination between mitochondrial motility and energy distribution. Therefore, we studied the impact of brain-type creatine kinase (CK-B) deficiency on transport activity and velocity of mitochondria in primary murine neurons and made a comparison to the fate of "metabolically inert" cargo, amyloid precursor protein (APP) in these cells, using live cell imaging.
Results: Comparison of average and maximum transport velocities showed that CK-B deficiency had no effect on speed of movement of mitochondria or APP cargo. Further analysis revealed, however, that the fraction of motile mitochondria was significantly increased by 35% in neurons derived from CK-B knockout mice.
Conclusion: CK-B activity does not directly determine motor protein activity for protein or organelle cargo transport but the fraction of motile mitochondria in cells without the enzyme is selectively increased. Possibly this serves as an adaptational strategy aimed to enhance mitochondrial distribution versatility in order to compensate for loss of efficiency in the cellular network for ATP supply.
Author: Jan WP Kuiper, Frank TJJ Oerlemans, Jack AM Fransen and Be Wieringa Credits/Source: BMC Neuroscience 2008, 9:73
Published on: 2008-07-28
Copyright by the authors listed above - made available via BioMedCentral (Open Access). Please
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