Development of the ovine model of NCL has been pivotal to our present understanding
of the ceroid lipofuscinoses. Analyses of isolated storage product have shown it to
be composed of identifiable chemical species of which subunit c of mitochondrial ATP
synthase is dominant (ca 50 %). It is an extremely hydrophobic protein and failure
to catabolise it may be associated with a propensity to form paracrystalline structures
with lipids that cannot be degraded by the normal complement of lysosomal enzymes.
However, the putative biochemical defect must be related to it and may reside within
the mitochondria. Multiple copies of subunit c help form the transmembrane Fo complex
which, with partially immobilised lipids, forms an Fo complex domain. This may need to be disassembled in an orderly fashion before proteolysis of subunit
c can occur. It is postulated that the primary defect may involve disassembly of the
Fo complex domain which may involve more than one step.
Subunit c - ATP synthase - Fo complex domain - Boundary lipids
