Decreased lysosomal subunit c-degrading activity in fibroblasts from patients with late infantile neuronal ceroid lipofuscinosis.
We investigated in in-vitro cell-free incubation experiments which factor, lysosomal proteolytic dysfunction or structural alteration of subunit c, is responsible for the specific delay in the degradation of subunit c in patient cells with the late infantile form of neuronal ceroid lipofuscinosis. Experiments using substrates and soluble lysosomal fractions isolated separately from control and patient cells indicated that lysosomes from control cells are able to degrade mitochondrial subunit c either from control or patient cells at much faster rate than lysosomes from patient cells. Subunit c stored in patient cell lysosomes showed much more resistance to proteolytic attack than mitochondrial subunit c, suggesting that conformation of subunit c as well as lysosomal proteolytic dysfunction both participate in the specific lysosomal accumulation of subunit c in the late infantile disease.
Ezaki
J
J
Department of Biochemistry, Juntendo University School of Medicine, Tokyo, Japan.
Wolfe
L S
LS
Kominami
E
E
D025181:ATP Synthetase Complexes; D000293:Adolescent; D001921:Brain / Q000201:enzymology; D002474:Cell-Free System; D002648:Child; D002675:Child, Preschool; D005347:Fibroblasts; D006801:Humans; D007223:Infant; D008247:Lysosomes / Q000201:enzymology; D008928:Mitochondria / Q000201:enzymology; D009097:Multienzyme Complexes / Q000378:metabolism*; D009472:Neuronal Ceroid-Lipofuscinoses / Q000201:enzymology*; D017856:Phosphotransferases (Phosphate Group Acceptor) / Q000378:metabolism*; D012016:Reference Values
D009097:Multienzyme Complexes; D025181:ATP Synthetase Complexes; D017856:Phosphotransferases (Phosphate Group Acceptor)