Batten disease (ceroid-lipofuscinosis): the enigma of subunit c of mitochondrial ATP synthase accumulation.

Abstract

Ceroid-lipofuscinosis is an inherited neurodegenerative disease of human beings and domestic animals characterized by the accumulation in neurons and other cells of a fluorescent lipopigment. In the ovine form of disease, subunit c of mitochondrial ATP synthase is the dominant accumulated metabolite ( > 50%). It also accumulates significantly in the late infantile and juvenile forms of the human disease and several other animal forms. Evidence is accumulating that the underlying biochemical defect may be associated with mitochondria. The extreme hydrophobicity of subunit c and its propensity to aggregate with lipids into regular multilamellar arrays that cannot be catabolised may reflect an initial defect not necessarily associated with faulty proteolysis. This hypothesis extends an earlier one that subunit c accumulated due to a defect in its catabolic pathway.