Kay 2000 J Biol Chem

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Kay L, Nicolay K, Wieringa B, Saks V, Wallimann T (2000) Direct evidence for the control of mitochondrial respiration by mitochondrial creatine kinase in oxidative muscle cells in situ. J Biol Chem 275:6937-44.

» PMID: 10702255 Open Access

Kay L, Nicolay K, Wieringa B, Saks V, Wallimann T (2000) J Biol Chem

Abstract: The efficiency of stimulation of mitochondrial respiration in permeabilized muscle cells by ADP produced at different intracellular sites, e.g. cytosolic or mitochondrial intermembrane space, was evaluated in wildtype and creatine kinase (CK)-deficient mice. To activate respiration by endogenous production of ADP in permeabilized cells, ATP was added either alone or together with creatine. In cardiac fibers, while ATP alone activated respiration to half of the maximal rate, creatine plus ATP increased the respiratory rate up to its maximum. To find out whether the stimulation by creatine is a consequence of extramitochondrial [ADP] increase, or whether it directly correlates with ADP generation by mitochondrial CK in the mitochondrial intermembrane space, an exogenous ADP-trap system was added to rephosphorylate all cytosolic ADP. Under these conditions, creatine plus ATP still increased the respiration rate by 2.5 times, compared with ATP alone, for the same extramitochondrial [ADP] of 14 mM. Moreover, this stimulatory effect of creatine, observed in wild-type cardiac fibers disappeared in mitochondrial CK deficient, but not in cytosolic CK-deficient muscle. It is concluded that respiration rates can be dissociated from cytosolic [ADP], and ADP generated by mitochondrial CK is an important regulator of oxidative phosphorylation.


O2k-Network Lab: CH Zurich Wallimann T, EE Tallinn Saks VA, FR Grenoble Saks VA, NL Eindhoven Nicolay K


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Organism: Mouse  Tissue;cell: Skeletal muscle  Preparation: Permeabilized cells, Permeabilized tissue 

Regulation: ADP, PCr;Cr  Coupling state: OXPHOS 

HRR: Oxygraph-2k