Mitochondrial affinity for ADP is twofold lower in creatine kinase knock-out muscles - Possible role in rescuing cellular energy homeostasis

F ter Veld*, JAL Jeneson, K Nicolay

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

11 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)956-965
Number of pages10
JournalFebs Journal
Volume272
Issue number4
DOIs
Publication statusPublished - Feb-2005

Keywords

  • heart
  • metabolic control
  • mitochondrial respiration
  • skeletal muscle
  • transgenic mice
  • HUMAN SKELETAL-MUSCLE
  • OXIDATIVE-PHOSPHORYLATION
  • DEFICIENT MUSCLES/
  • HEART-MITOCHONDRIA
  • KINETIC-PROPERTIES
  • RAT LIVER
  • MICE
  • ISOENZYMES
  • MEMBRANE
  • COMPARTMENTATION

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