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 familial and 5 sporadic cases) suffering from myopathies with TAs. In muscle biopsy specimens from 5 of the 7 patients, TAs were immunopositive for the ryanodine receptor (RYR 1) of the sarcoplasmic reticulum (SR), the SR Ca2+ pump (SERCA2-ATPase), and the intraluminal SR Ca2+ binding protein calsequestrin, indicating an SR origin of these aggregates. Furthermore, these 5 cases showed decreased respiratory chain enzyme activities (NADH:CoQ oxidoreductase. complex I and cytochrome c oxidase [COX], complex IV), while the remaining 2 patients exhibited normal values. Our findings indicate a functional link between mitochondrial dysfunction and the presence of TAs originating from the sarcoplasmic reticulum.
Vielhaber
S
S
Department of Neurology, Otto-von-Guericke-University Magdeburg, Germany.
Schröder
R
R
Winkler
K
K
Weis
S
S
Sailer
M
M
Feistner
H
H
Heinze
H J
HJ
Schröder
J M
JM
Kunz
W S
WS
D000328:Adult; D001706:Biopsy; D000252:Calcium-Transporting ATPases / Q000032:analysis / Q000276:immunology; D002155:Calsequestrin / Q000032:analysis / Q000276:immunology; D019069:Cell Respiration; D004272:DNA, Mitochondrial / Q000032:analysis; D004734:Energy Metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D017240:Mitochondrial Myopathies / Q000378:metabolism* / Q000473:pathology*; D018485:Muscle Fibers, Skeletal / Q000737:chemistry / Q000201:enzymology / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D010085:Oxidative Phosphorylation; D019837:Ryanodine Receptor Calcium Release Channel / Q000032:analysis / Q000276:immunology; D012503:Saponins; D012519:Sarcoplasmic Reticulum / Q000378:metabolism* / Q000473:pathology*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D017186:Titrimetry
D002155:Calsequestrin; D004272:DNA, Mitochondrial; D019837:Ryanodine Receptor Calcium Release Channel; D012503:Saponins; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506946:ATP2A2 protein, human; D000252:Calcium-Transporting ATPases