Some new aspects of creatine kinase (CK): compartmentation, structure, function and regulation for cellular and mitochondrial bioenergetics and physiology
Affiliations: Institute of Cell Biology, ETH‐Hönggerberg, CH‐8093 Zürich, Switzerland | Faculty of Biology, University of Konstanz, D‐78457 Konstanz, Germany
Note: [] Corresponding author: Theo Wallimann, Institute of Cell Biology, ETH‐Hönggerberg, CH‐8093 Zürich, Switzerland. Tel.: +41 1 633 33 92; Fax: +41 1 633 10 69; E‐mail: [email protected].
Note: [] Present address: School of Biological Sciences, University of Manchester, Manchester M13 9PT, UK.
Abstract: Creatine kinase (CK) isoenzymes, specifically located at places of energy demand and energy production, are linked by a phosphocreatine/creatine (PCr/Cr) circuit, found in cells with intermittently high energy demands. Cytosolic CKs, in close conjunction with Ca^{2+}‐pumps, play a crucial role for the energetics of Ca^{2+}‐homeostasis. Mitochondrial Mi‐CK, a cuboidal‐shaped octamer with a central channel, binds and crosslinks mitochondrial membranes and forms a functionally coupled microcompartment with porin and adenine nucleotide translocase for vectorial export of PCr into the cytosol. The CK system is regulated by AMP‐activated protein kinase via PCr/Cr and ATP/AMP ratios. Mi‐CK stabilizes and cross‐links cristae‐ or inner/outer membranes to form parallel membrane stacks and, if overexpressed due to creatine depletion or cellular energy stress, forms those crystalline intramitochondrial inclusions seen in some mitochondrial cytopathy patients. Mi‐CK is a prime target for free radical damage by peroxynitrite. Mi‐CK octamers, together with CK substrates have a marked stabilizing and protective effect against mitochondrial permeability transition pore opening, thus providing a rationale for creatine supplementation of patients with neuromuscular and neurodegenerative diseases.
Keywords: Creatine kinase (CK), phosphocreatine shuttle, energetics of Ca[TeX:] ^{2+}‐homeostasis, CK null mutant transgenic mice, mitochondrial creatine kinase (Mi‐CK), intramitochondrial inclusions, mitochondrial myopathies, AMP‐activated protein kinase, mitochondrial permeability transition, peroxynitrite, porin, adenine nucleotide translocase (ANT), cell‐ and neuroprotective effects of creatine, creatine supplementation, neuromuscular diseases
Journal: Biofactors, vol. 8, no. 3-4, pp. 229-234, 1998
