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Some new aspects of creatine kinase (CK): compartmentation, structure, function and regulation for cellular and mitochondrial bioenergetics and physiology
Author(s) -
Wallimann Theo,
Dolder Max,
Schlattner Uwe,
Eder Michael,
Hornemann Thorsten,
O'Gorman Eddie,
Rück Alex,
Brdiczka Dieter
Publication year - 1998
Publication title -
biofactors
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.204
H-Index - 94
eISSN - 1872-8081
pISSN - 0951-6433
DOI - 10.1002/biof.5520080310
Subject(s) - phosphocreatine , voltage dependent anion channel , creatine kinase , cytosol , mitochondrion , bioenergetics , creatine , microbiology and biotechnology , mitochondrial permeability transition pore , inner mitochondrial membrane , biochemistry , adenosine triphosphate , adenine nucleotide , biology , biophysics , energy metabolism , nucleotide , bacterial outer membrane , programmed cell death , enzyme , apoptosis , endocrinology , escherichia coli , gene
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.