Bovine ceroid-lipofuscinosis (Batten's disease): The major component stored is the DCCD-reactive proteolipid, subunit c, of mitochondrial ATP synthase

Abstract

The ceroid-lipofuscinoses (Batten's disease) are a group of recessively inherited lysosomal storage diseases of children and animals in which there is intracellular accumulation of a fluorescent lipopigment in a wide variety of cells. Lipopigment bodies isolated from pancreas, liver, kidney and brain tissue from a heifer affected with ceroid-lipofuscinosis contained between 55 and 62% protein. A dominant component comigrated on LDS-PAGE with the major low molecular weight protein stored in ovine ceroid-lipofuscinosis. It was identified by amino acid sequence and mass spectroscopy as the full subunit c of mitochondrial ATP synthase, normally found only in the inner mitochondrial membrane, where it is estimated to account for 2-4% of the membrane protein. In pancreatic lipopigment it accounted for at least 40% of the total lipopigment mass and this storage was considered specific to the disease. No other mitochondrial proteins were found in storage bodies. These results are similar to those found in studies on the ovine and the late infantile and juvenile human forms of the disease. It is concluded that bovine ceroid-lipofuscinosis is also a proteolipid proteinosis in which subunit c of mitochondrial ATP synthase is specifically stored in lysosome derived organelles.

Neuronal pigmented autophagic vacuoles: lipofuscin, neuromelanin, and ceroid as macroautophagic responses during aging and disease

“…2004). It is normally found only in the inner mitochondrial membrane, where it accounts for 2–4% of protein, but may compromise 40% of ceroid in Batten disease and in cattle and horse NCLs (Martinus et al. 1991).…”

Selectivity and Types of Cell Death in the Neuronal Ceroid Lipofuscinoses (NCLs)

“…Large animal models of NCL. As comprehensively reviewed elsewhere (46,49,63), an NCL-like phenotype has been described in a number of larger domestic animal species including canine (45,53,65,75,93), ovine (12,43,44,73,92), equine (99) and bovine (36,66) species. ese large animal models offer significant advantages over their murine counterparts, with a more complex CNS and a prolonged time course to study disease progression.…”

Variant proteins in ovine ceroid‐lipofuscinosis

“…Accumulation of subunit c of the mitochondrial inner membrane Fo portion of ATP synthase occurs in a number of the ceroid-lipofuscinoses [Palmer et al, 1989[Palmer et al, , 1992Fearnley et al, 1990;Martinus et al, 1991;Faust et al, 19941. The basis of subunit c storage is obscure, as the nuclear genes coding for this protein are normal, as are the mRNA levels [Medd et al, 19931.…”