Open AccessMitochondrial creatine kinase: a major constituent of pathological inclusions seen in mitochondrial myopathies.
Author(s) -
A. M. Stadhouders,
P. H. K. Jap,
Hanspeter Winkler,
Hans M. Eppenberger,
Theo Wallimann
Publication year - 1994
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.91.11.5089
Subject(s) - mitochondrion , mitochondrial encephalomyopathies , mitochondrial myopathy , creatine kinase , electron microscope , mitochondrial dna , chemistry , crystallography , biology , anatomy , pathology , microbiology and biotechnology , biochemistry , medicine , physics , optics , gene
Overaccumulation of abnormally organized mitochondria in so-called "ragged-red" skeletal muscle fibers is a morphological hallmark of mitochondrial myopathies, in particular of mitochondrial encephalomyopathies. Characteristic for the abnormal mitochondria is the occurrence of highly ordered crystalline inclusions. Immuno-electron microscopy revealed that these inclusions react heavily with specific antibodies against mitochondrial creatine kinase (Mi-CK). Image processing of selected crystalline inclusions, sectioned along the crystallographic b, c planes, resulted in an averaged picture displaying an arrangement of regular, square-shaped particles with a central cavity. The overall appearance, dimensions, and symmetry of these building blocks are very reminiscent of single isolated Mi-CK octamers. Taking these findings together, it is concluded that Mi-CK octamers indeed represent the major, if not the only, component of these mitochondrial inclusions.