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首页> 外文期刊>The FEBS journal >Mitochondrial affinity for ADP is twofold lower in creatine kinase knock-out muscles - Possible role in rescuing cellular energy homeostasis
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Mitochondrial affinity for ADP is twofold lower in creatine kinase knock-out muscles - Possible role in rescuing cellular energy homeostasis

机译：在肌酸激酶敲除肌肉中，线粒体对ADP的亲和力低两倍-可能在拯救细胞能量稳态中发挥作用

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摘要

Adaptations of the kinetic properties of mitochondria in striated muscle lacking cytosolic (M) and/or mitochondrial (Mi) creatine kinase (CK) isoforms in comparison to wild-type (WT) were investigated in vitro. Intact mitochondria were isolated from heart and gastrocnemius muscle of WT and single- and double CK-knock-out mice strains (cytosolic (M-CK-/-), mitochondrial (Mi-CK-/-) and double knock-out (MiM-CK-/-) respectively). Maximal ADP-stimulated oxygen consumption flux (State3 V-max; nmol O-2.mg mitochondrial protein(-1).min(-1)) and ADP affinity (K-50(ADP); muM) were determined by respirometry. State 3 V-max and K-50(ADP) of M-CK-/- and MiM-CK-/- gastrocnemius mitochondria were twofold higher than those of WT, but were unchanged for Mi-CK-/-. For mutant cardiac mitochondria, only the K-50(ADP) of mitochondria isolated from the MiM-CK-/- phenotype was different (i.e. twofold higher) than that of WT. The implications of these adaptations for striated muscle function were explored by constructing force-flow relations of skeletal muscle respiration. It was found that the identified shift in affinity towards higher ADP concentrations in MiM-CK-/- muscle genotypes may contribute to linear mitochondrial control of the reduced cytosolic ATP free energy potentials in these phenotypes.
机译：与野生型（WT）相比，缺乏细胞质（M）和/或线粒体（Mi）肌酸激酶（CK）亚型的横纹肌中线粒体动力学特性的适应性进行了研究。完整的线粒体分离自野生型小鼠的心脏和腓肠肌以及单和双CK敲除小鼠品系（胞质（M-CK-/-），线粒体（Mi-CK-/-）和双敲除（MiM） -CK-/-））。通过呼吸测定法测定最大ADP刺激的耗氧通量（State3 V-max; nmol O-2.mg线粒体蛋白（-1）.min（-1））和ADP亲和力（K-50（ADP）; muM）。 M-CK-/-和MiM-CK-/-腓肠肌线粒体的状态3 V-max和K-50（ADP）比野生型高2倍，但Mi-CK-/-不变。对于突变的心脏线粒体，仅从MiM-CK-/-表型分离的线粒体的K-50（ADP）与WT的线粒体不同（即高两倍）。通过构建骨骼肌呼吸的力流关系，探索了这些适应对横纹肌功能的影响。已发现，在MiM-CK-/-肌肉基因型中，朝着较高ADP浓度的亲和力转变可能有助于线性线粒体控制这些表型中降低的胞质ATP自由能。

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