LATE-INFANTILE CEROID-LIPOFUSCINOSIS - LYSINE METHYLATION OF MITOCHONDRIAL ATP SYNTHASE SUBUNIT-C FROM LYSOSOMAL STORAGE BODIES

Late-infantile ceroid-lipofuscinosis is a fatal autosomal recessively inherited disease characterized by massive accumulations of lysosomal storage bodies in many tissues. A major constituent of the storage bod ies is the subunit c protein of mitochondrial ATP synthase. Juvenile c eroid-lipofuscinosis, a disease that is similar to but genetically dis tinct from the late-infantile disorder, also involves lysosomal accumu lation of the subunit c protein. In the juvenile disease, the stored f orm of the protein contains an epsilon-N-trimethyllysine (TML) residue at position 43. Analyses were performed to determine whether subunit c protein stored in the late-infantile disease is also trimethylated a t lysine residue 43. Amino acid composition analysis of the subunit c protein stored in brains from subjects with the late-infantile disease indicated that one of the two lysine residues in the protein is trime thylated. Data from molecular mass analysis of the protein was consist ent with the presence of three methyl groups not present in the unmodi fied protein. The TML in the storage body subunit c protein was found by amino acid sequence analysis to occur exclusively at residue 43. Th e lysine at this position in the stored protein was completely methyla ted. Recent studies suggest that the subunit c protein from normal mit ochondria may also have the same amino acid modification. Thus, it app ears that specific methylation of lysine residue 43 of mitochondrial A TP synthase subunit c is probably a normal post-translational modifica tion, and that the lysosomal storage of this protein in late-infantile , as well as in juvenile ceroid-lipofuscinosis, does not result from a defect in its methylation.