SPECIFIC DELAY OF DEGRADATION OF MITOCHONDRIAL ATP SYNTHASE SUBUNIT-CIN LATE INFANTILE NEURONAL CEROID-LIPOFUSCINOSIS (BATTEN-DISEASE)

Subunit c is normally present as an inner mitochondrial membrane compo nent of the F-o section of the ATP synthase complex, but in the late i nfantile form of neuronal ceroid lipofuscinosis (NCL) it was also foun d in lysosomes in high concentrations. To explore the mechanism of sto rage of subunit c, the rates of degradation and synthesis of subunit c were measured in fibroblast cell types from controls and patients wit h the late infantile form of NCL. The radiolabel from subunit c decrea sed with time in control cells, whereas no apparent loss of radioactiv ity of subunit c was found in patients' cells. There were no significa nt differences between control cells and cells with disease in the deg radation of cytochrome oxidase subunit IV, an inner membrane protein o f mitochondria. A combination of pulse-chase and subcellular fractiona tion analysis showed that a delay of intramitochondrial loss from prel abeled subunit c was seen in all diseased cells tested. Lysosomal appe arance of labeled subunit c could be detected after chase for more tha n 1 week and its radioactivities were variable among diseased cell typ es. The biosynthetic rate of subunit c was almost the same in both con trol and patient cells. Northern blotting analyses showed that mRNAs f or P1 and P2 genes had no significant difference in lengths and amount s between control and patient cells. Results suggest a specific failur e in the degradation of subunit c after its normal inclusion in mitoch ondria and its consequent accumulation in lysosomes. This is the first direct evidence to show a delay of subunit c degradation in the cells from the late infantile form of NCL.