MITOCHONDRIAL CREATINE-KINASE - A MAJOR CONSTITUENT OF PATHOLOGICAL INCLUSIONS SEEN IN MITOCHONDRIAL MYOPATHIES

Overaccumulation of abnormally organized mitochondria in so-called ''r agged-red'' skeletal muscle fibers is a morphological hallmark of mito chondrial myopathies, in particular of mitochondrial encephalomyopathi es. Characteristic for the abnormal mitochondria is the occurrence of highly ordered crystalline inclusions. Immune-electron microscopy reve aled that these inclusions react heavily with specific antibodies agai nst mitochondrial creatine kinase (ML-CK). Image processing of selecte d crystalline inclusions, sectioned along the crystallographic b, c pl anes, resulted in an averaged picture displaying an arrangement of reg ular, square-shaped particles with a central cavity. The overall appea rance, dimensions, and symmetry of these budding blocks are very remin iscent of single isolated Mi-CK octamers. Taking these findings togeth er, it is concluded that Mi-CK octamers indeed represent the major, if not the only, component of these mitochondrial inclusions.