Mitochondrial Creatine Kinase: A Major Constituent of Pathological Inclusions Seen in Mitochondrial Myopathies

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 91; no. 11; pp. 5089 - 5093
• Main Authors: Stadhouders, Ad M., Paul H. K. Jap, Winkler, Hans-Peter, Eppenberger, Hans M., Wallimann, Theo
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 24.05.1994; National Acad Sciences; National Academy of Sciences
• Subjects: Antibodies; Biopsies; Cellular biology; Creatine; creatine kinase; Creatine Kinase - metabolism; Crystals; encephalomyopathy; Enzymes; Humans; Image processing; Inclusion Bodies - ultrastructure; Inclusions; man; Microscopy, Immunoelectron; Mitochondria; Mitochondria - enzymology; Mitochondria - ultrastructure; Mitochondrial myopathies; Mitochondrial Myopathies - enzymology; Mitochondrial Myopathies - pathology; Muscular system; Pathology; ragged-red fibers; skeletal muscle
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.91.11.5089

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.