Octameric mitochondrial creatine kinase induces and stabilizes contact sites between the inner and outer membrane.

We have investigated the role of the protein ubiquitous mitochondrial creatine kinase (uMtCK) in the formation and stabilization of inner and outer membrane contact sites. Using liver mitochondria isolated from transgenic mice, which, unlike control animals, express uMtCK in the liver, we found that the enzyme was associated with the mitochondrial membranes and, in addition, was located in membrane-coated matrix inclusions. In mitochondria isolated from uMtCK transgenic mice, the number of contact sites increased 3-fold compared with that observed in control mitochondria. Furthermore, uMtCK-containing mitochondria were more resistant to detergent-induced lysis than wild-type mitochondria. We conclude that octameric uMtCK induces the formation of mitochondrial contact sites, leading to membrane cross-linking and to an increased stability of the mitochondrial membrane architecture.

[1]  Theo Wallimann,et al.  C-terminal Lysines Determine Phospholipid Interaction of Sarcomeric Mitochondrial Creatine Kinase* , 2004, Journal of Biological Chemistry.

[2]  T. Wallimann,et al.  Inhibition of the Mitochondrial Permeability Transition by Creatine Kinase Substrates , 2003, The Journal of Biological Chemistry.

[3]  D. Newmeyer,et al.  Mitochondria Releasing Power for Life and Unleashing the Machineries of Death , 2003, Cell.

[4]  D. Brdiczka,et al.  The Function of Complexes between the Outer Mitochondrial Membrane Pore (vdac) and the Adenine Nucleotide Translocase in Regulation of Energy Metabolism and Apoptosis , 2003 .

[5]  T. Wallimann,et al.  Novel Mitochondrial Creatine Transport Activity , 2002, The Journal of Biological Chemistry.

[6]  A. Reichert,et al.  Contact sites between the outer and inner membrane of mitochondria-role in protein transport. , 2002, Biochimica et biophysica acta.

[7]  Theo Wallimann,et al.  Multiple interference of anthracyclines with mitochondrial creatine kinases: preferential damage of the cardiac isoenzyme and its implications for drug cardiotoxicity. , 2002, Molecular pharmacology.

[8]  A. Koretsky,et al.  Transgenic livers expressing mitochondrial and cytosolic CK: mitochondrial CK modulates free ADP levels. , 2002, American journal of physiology. Cell physiology.

[9]  T. Wallimann,et al.  Mitochondrial Creatine Kinase and Mitochondrial Outer Membrane Porin Show a Direct Interaction That Is Modulated by Calcium* , 2001, The Journal of Biological Chemistry.

[10]  M. Wyss,et al.  Creatine and creatinine metabolism. , 2000, Physiological reviews.

[11]  T. Wallimann,et al.  Octamers of Mitochondrial Creatine Kinase Isoenzymes Differ in Stability and Membrane Binding* , 2000, The Journal of Biological Chemistry.

[12]  W. Kabsch,et al.  Crystal structure of human ubiquitous mitochondrial creatine kinase , 2000, Proteins.

[13]  G J Brewer,et al.  Protective Effect of the Energy Precursor Creatine Against Toxicity of Glutamate and β‐Amyloid in Rat Hippocampal Neurons , 2000, Journal of neurochemistry.

[14]  B. Wieringa,et al.  Direct Evidence for the Control of Mitochondrial Respiration by Mitochondrial Creatine Kinase in Oxidative Muscle Cells in Situ * , 2000, The Journal of Biological Chemistry.

[15]  T. Wallimann,et al.  A Quantitative Approach to Membrane Binding of Human Ubiquitous Mitochondrial Creatine Kinase Using Surface Plasmon Resonance , 2000, Journal of bioenergetics and biomembranes.

[16]  P. Bernardi,et al.  Mitochondrial transport of cations: channels, exchangers, and permeability transition. , 1999, Physiological reviews.

[17]  U. Rüegg,et al.  Creatine supplementation improves intracellular Ca2+ handling and survival in mdx skeletal muscle cells , 1998, FEBS letters.

[18]  E. Fontaine,et al.  Chemical Modification of Arginines by 2,3-Butanedione and Phenylglyoxal Causes Closure of the Mitochondrial Permeability Transition Pore* , 1998, The Journal of Biological Chemistry.

[19]  D. Brdiczka,et al.  Complexes between porin, hexokinase, mitochondrial creatine kinase and adenylate translocator display properties of the permeability transition pore. Implication for regulation of permeability transition by the kinases. , 1998, Biochimica et biophysica acta.

[20]  T. Wallimann,et al.  The molecular structure of mitochondrial contact sites. Their role in regulation of energy metabolism and permeability transition , 1998, BioFactors.

[21]  A. Koretsky,et al.  The role of creatine kinase in inhibition of mitochondrial permeability transition , 1997, FEBS letters.

[22]  P. Tittmann,et al.  Crystalline mitochondrial inclusion bodies isolated from creatine depleted rat soleus muscle. , 1997, Journal of cell science.

[23]  A. Koretsky,et al.  Expression of functional mitochondrial creatine kinase in liver of transgenic mice. , 1997, The American journal of physiology.

[24]  D. Brdiczka,et al.  Complexes between hexokinase, mitochondrial porin and adenylate translocator in brain: regulation of hexokinase, oxidative phosphorylation and permeability transition pore. , 1997, Biochemical Society transactions.

[25]  T. Wallimann,et al.  Membrane-binding and lipid vesicle cross-linking kinetics of the mitochondrial creatine kinase octamer. , 1996, Biochemistry.

[26]  W. Welte,et al.  Complexes between kinases, mitochondrial porin and adenylate translocator in rat brain resemble the permeability transition pore , 1996, FEBS letters.

[27]  H. Eppenberger,et al.  Mitochondrial creatine kinase: a major constituent of pathological inclusions seen in mitochondrial myopathies. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[28]  H. Eppenberger,et al.  Creatine Kinase Isoenzymes in Chicken Cerebellum: Specific Localization of Brain‐type Creatine Kinase in Bergmann Glial Cells and Muscle‐type Creatine Kinase in Purkinje Neurons , 1994, The European journal of neuroscience.

[29]  G. Griffiths.  Cryo and Replica Techniques for Immunolabelling , 1993 .

[30]  M. Wyss,et al.  Mitochondrial creatine kinase: a key enzyme of aerobic energy metabolism. , 1992, Biochimica et biophysica acta.

[31]  M. Wyss,et al.  Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: the 'phosphocreatine circuit' for cellular energy homeostasis. , 1992, The Biochemical journal.

[32]  T. Wallimann,et al.  Mitochondrial creatine kinase mediates contact formation between mitochondrial membranes. , 1991, The Journal of biological chemistry.

[33]  H. Eppenberger,et al.  Differential expression and localization of brain-type and mitochondrial creatine kinase isoenzymes during development of the chicken retina: Mi-CK as a marker for differentiation of photoreceptor cells. , 1991, Differentiation; research in biological diversity.

[34]  T. Wallimann,et al.  Location and regulation of octameric mitochondrial creatine kinase in the contact sites. , 1991, Biochimica et biophysica acta.

[35]  P. Louisot,et al.  Further characterization of mitochondrial contact sites: effect of short-chain alcohols on membrane fluidity and activity. , 1990, Biochemical and biophysical research communications.

[36]  D. Vestweber,et al.  Protein import into mitochondria: ATP-dependent protein translocation activity in a submitochondrial fraction enriched in membrane contact sites and specific proteins , 1989, The Journal of cell biology.

[37]  T. Wallimann,et al.  Further characterization of contact sites from mitochondria of different tissues: topology of peripheral kinases. , 1989, Biochimica et biophysica acta.

[38]  P J Geiger,et al.  Transport of energy in muscle: the phosphorylcreatine shuttle. , 1981, Science.