Sm. Hughes et al., Submitochondrial distribution and delayed proteolysis of subunit c of the H+-transporting ATP-synthase in ovine ceroid-lipofuscinosis, ELECTROPHOR, 22(9), 2001, pp. 1785-1794
The neuronal ceroid-lipofuscinose (NCL) are recessively inherited lysosomal
storage diseases in children and animals. The major stored protein in many
of these diseases is subunit c of the mitochondrial inner membrane H+-tran
sporting ATP-synthase. Previous studies of naturally occurring ovine ceroid
-lipofuscinosis (OCL) in South Hampshire sheep showed that the genes and tr
anscripts for subunit c were normal and inferred that this protein was expr
essed normally in mitochondria prior to storage in lysosomes. Accumulation
in mitochondria has not been conclusively established and we have therefore
used the South Hampshire model to demonstrate approximately 1.8-fold norma
l levels of subunit c in mitochondrial inner membranes prepared from liver.
Other mitochondrial inner membrane and ATP-synthase proteins that could be
detected by mass spectrometry (MS) or two-dimensional electrophoresis (2-D
E) were present in normal amounts. The accumulating subunit c showed normal
post-translational modification but was abnormally resistant to proteolysi
s. These results are consistent with the hypothesis that OCL may result fro
m a mitochondrial disorder that affects turnover of correctly expressed sub
unit c, although we cannot exclude the possibility that a postmitochondrial
defect delays processing of subunit c out of mitochondria.