Nedergaard 2017 MiP2017
Mitochondria were isolated from C57Bl/6 mice that were single-caged, acclimated for 2 weeks at 18°C and then at 4°C for at least 4 weeks. Prolonged cold exposure turns inguinal white adipose into UCP1-contaning brite/beige adipose tissue. Oxygen consumption of isolated mitochondria was analyzed with Oroboros O2k-FluoRespirometer.
Creatine (20 mM) added to heart mitochondria after ADP phosphorylation drastically increased oxygen consumption, presumably by ADP released from ATP when high-energy phosphoryl group from ATP was transferred to phosphocreatine. This phenomenon is well described  and explained by functional coupling of mitochondrial creatine kinase (sarcomeric isoform) and adenine nucleotide translocase and catalysed transfer of phosphoryl groups from ATP generated by OxPhosph with phosphocreatine production. In liver mitochondria, the enhancing effect of creatine was absent; this is well correlated with tissue distribution of sarcomeric creatine kinase. Brown and brite/beige adipose tissue mitochondria are unique in extremely low capacity of phosphorylation system  and the presence of highly active sarcomeric creatine kinase looks incompatible with the low phosphorylation activity. However, we were able to shown creatine-enhancing effects in brown fat mitochondria similarly to heart mitochondria. Creatine effect was observed only under high concentration (15-30 mM). We were not able to demonstrate that low creatine (0.01 mM) enhances respiration in beige-fat mitochondria when ADP is limiting.
Our results show that in the presence of ATP and ADP, high concentration of creatine enhanced oxygen consumption in mitochondria containing the sarcomeric isoform of creatine kinase, independently of high or low OxPhosph capacity.
Labels: MiParea: Respiration, mt-Medicine, Pharmacology;toxicology
Organism: Mouse Tissue;cell: Heart, Liver, Fat Preparation: Isolated mitochondria
Dept Molecular Bioscience, Wenner-Gren Inst, Stockholm Univ, Sweden. - firstname.lastname@example.org
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