title: Creatine kinase B deficient neurons exhibit an increased fraction of motile mitochondria.
abstract: BACKGROUND
  Neurons require an elaborate system of intracellular transport to distribute cargo throughout axonal and dendritic projections. Active anterograde and retrograde transport of mitochondria serves in local energy distribution, but at the same time also requires 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 analysed 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 amyloid precursor protein (APP) cargo in these cells, using live cell imaging.
  
  
  RESULTS
  Comparison of average and maximum transport velocities and global transport activity showed that CK-B deficiency had no effect on speed of movement of mitochondria or APP cargo, but that the fraction of motile mitochondria was significantly increased by 36% in neurons derived from CK-B knockout mice. The percentage of motile APP vesicles was not altered.
  
  
  CONCLUSIONS
  CK-B activity does not directly couple to motor protein activity but cells without the enzyme increase the number of motile mitochondria, possibly as an adaptational strategy aimed to enhance mitochondrial distribution versatility in order to compensate for loss of efficiency in the cellular network for ATP distribution.
authors.affiliation: Department of Cell Biology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. j.kuiper@ncmls.ru.nl
authors.forename: Jan W P
authors.initials: JW
authors.lastname: Kuiper
authors.forename: Frank T J J
authors.initials: FT
authors.lastname: Oerlemans
authors.forename: Jack A M
authors.initials: JA
authors.lastname: Fransen
authors.forename: Bé
authors.initials: B
authors.lastname: Wieringa
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001370:Axonal Transport / Q000502:physiology; D002478:Cells, Cultured; D052276:Creatine Kinase, BB Form / Q000172:deficiency* / Q000235:genetics; D004734:Energy Metabolism; D019084:Fluorescent Antibody Technique, Indirect / Q000379:methods; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D008164:Luminescent Proteins; D011993:Recombinant Fusion Proteins; D052276:Creatine Kinase, BB Form