Defective mitochondrial oxidative phosphorylation in myopathies with tubular aggregates originating from sarcoplasmic reticulum

Abnormalities of the sarcotubular system presenting as tubular aggregates ( TAs) have been described in a variety of neuromuscular disorders. Here, we report on immunohistochemical and biochemical findings in 7 patients (2 fam ilial and 5 sporadic cases) suffering from myopathies with TAs. In muscle b iopsy specimens front 5 of the 7 patients. TAs were immunopositive for the ryanodine receptor (RYR 1) of the sarcoplasmic reticulum (SR), the SR Ca2pump (SFRCA2-ATPase), and the intraluminal SR Ca2+ binding protein calseque strin, indicating ail SR origin of these aggregates. Furthermore, these 5 c ases showed decreased respiratory chain enzyme activities (NADH:CoQ oxidore ductase. complex I and cytochrome c oxidase [COX], complex IV), while the r emaining 2 patients exhibited normal values. Our findings indicate a functi onal link between mitochondrial dysfunction and the presence of TAs origina ting from tile sarcoplasmic reticulum.