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- Title
Some new aspects of creatine kinase (CK): compartmentation, structure, function and regulation for cellular and mitochondrial bioenergetics and physiology.
- Authors
Wallimann, T; Dolder, M; Schlattner, U; Eder, M; Hornemann, T; O'Gorman, E; Rück, A; Brdiczka, D
- 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.
- Publication
BioFactors (Oxford, England), 1998, Vol 8, Issue 3-4, p229
- ISSN
0951-6433
- Publication type
Journal Article
- DOI
10.1002/biof.5520080310