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キーワード:
Spinal muscular atrophy · Neurogenic muscular atrophy · Mitochondrial DNA depletion · Respiratory chain enzymes · Mitochondria
要旨:
Spinal muscular atrophy (SMA) is a neuromus-
cular disorder in childhood leading to a dramatic loss of
muscle strength. Functional investigations with high-reso-
lution polarography and enzyme measurements of the res-
piratory chain revealed lowered activities in muscle tissue
of SMA patients. To gain a better understanding of this
low energy supply we analyzed the amount of mitochon-
drial DNA (mtDNA) in skeletal muscle of 20 unrelated
children with genetically proven SMA and 31 controls.
Quantitative Southern blot analysis revealed a severe and
homogeneous decrease in the content of muscle mtDNA
in relation to nuclear DNA in SMA patients (90.3±7.8%),
whereas by immunofluorescence no decrease in the num-
ber of mitochondria was detected. In addition, a two- to
threefold reduction of the nuclear-encoded complex II
(succinate dehydrogenase) activity was detected in SMA
muscle tissue. Western blot analysis showed a significant
reduction of both mitochondrial- and nuclear-encoded cy-
tochrome c oxidase subunits. Our results indicate that
mtDNA depletion in SMA is a consequence of severe at-
rophy, and has to be differentiated by measurement of
complex II from an isolated reduction of mtDNA as found
in patients with mitochondriocytopathies and the so-
called mtDNA depletion syndrome.
