Monge 2008 Mol Cell Biochem
|Monge C, Beraud N, Kuznetsov AV, Rostovtseva T, Sackett D, Schlattner U, Vendelin M, Saks V (2008) Regulation of respiration in brain mitochondria and synaptosomes: restrictions of ADP diffusion in situ, roles of tubulin, and mitochondrial creatine kinase. Mol Cell Biochem 318:147-65.|
Abstract: The role of ubiquitous mitochondrial creatine kinase (uMtCK) reaction in regulation of mitochondrial respiration was studied in purified preparations of rat brain synaptosomes and mitochondria. In permeabilized synaptosomes, apparent Km for exogenous ADP, Km (ADP), in regulation of respiration in situ was rather high (110 ± 11lM) in comparison with isolated brain mitochondria (9 ± 1 lM). This apparent Km for ADP observed in isolated mitochondria in vitro dramatically increased to 169 ± 52lM after their incubation with 1 lM of dimeric tubulin showing that in rat brain, particularly in synaptosomes, mitochondrial outer membrane permeability for ADP, and ATP may be restricted by tubulin binding to voltage dependent anion channel (VDAC). On the other hand, in synaptosomes apparent Km (ADP) decreased to 25 ± 1 lM in the presence of 20 mM creatine. To fully understand this effect of creatine on kinetics of respiration regulation, complete kinetic analysis of uMtCK reaction in isolated brain mitochondria was carried out. This showed that oxidative phosphorylation specifically altered only the dissociation constants for MgATP, by decreasing that from ternary complex MtCK.Cr.MgATP (Ka) from 0.13 ± 0.02 to 0.018 ± 0.007 mMand that frombinary complexMtCK.MgATP (Kia) from 1.1 ± 0.29 mM to 0.17 ± 0.07 mM. Apparent decrease of dissociation constants for MgATP reflects effective cycling of ATP and ADP between uMtCK and adenine nucleotide translocase (ANT). These results emphasize important role and various pathophysiological implications of the phosphocreatine–creatine kinase systemin energy transfer in brain cells, including synaptosomes.
• Keywords: Brain, Creatine kinase, Functional coupling, Mitochondria, Synaptosomes, Tubulin
Labels: MiParea: Respiration
Stress:Mitochondrial disease Organism: Rat Tissue;cell: Nervous system Preparation: Isolated mitochondria