Mitochondrial ATP synthase subunit c stored in hereditary ceroid-lipofuscinosis contains trimethyl-lysine

• Published in: Biochemical journal Vol. 310; no. 3; pp. 887 - 892
• Main Authors: Katz, M L, Gao, C L, Tompkins, J A, Bronson, R T, Chin, D T
• Format: Journal Article
• Language: English
• Published: England 15.09.1995
• Subjects: Adolescent; Adult; Amino Acid Sequence; Animals; Autopsy; Brain - enzymology; Brain - pathology; Cytoplasmic Granules - enzymology; Cytoplasmic Granules - pathology; Cytoplasmic Granules - ultrastructure; Electrophoresis, Polyacrylamide Gel; Humans; Lysine - analogs & derivatives; Lysine - analysis; Macromolecular Substances; Mice; Mitochondria - enzymology; Molecular Sequence Data; Neuronal Ceroid-Lipofuscinoses - enzymology; Neuronal Ceroid-Lipofuscinoses - genetics; Neuronal Ceroid-Lipofuscinoses - veterinary; Proton-Translocating ATPases - chemistry; Proton-Translocating ATPases - genetics; Proton-Translocating ATPases - isolation & purification; Rodent Diseases; Sheep; Sheep Diseases
• ISSN: 0264-6021; 1470-8728
• DOI: 10.1042/bj3100887

The subunit c protein of mitochondrial ATP synthase accumulates in lysosomal storage bodies of numerous tissues in human subjects with certain forms of ceroid-lipofuscinosis, a degenerative hereditary disease. Subunit c appears to constitute a major fraction of the total storage-body protein. Lysosomal accumulation of subunit c has also been reported in putative animal models (dogs, sheep and mice) for ceroid-lipofuscinosis. In humans with the juvenile form of the disease, hydrolysates of total storage-body protein have been found to contain significant amounts of epsilon-N-trimethyl-lysine (TML). TML is also abundant in storage-body protein hydrolysates from affected dogs and sheep. These findings suggested that one or both of the two lysine residues of subunit c might be methylated in the stored form of the protein. The normal subunit c protein from mitochondria does not appear to be methylated. In a putative canine model for human juvenile ceroid-lipofuscinosis, residue 43 of the storage-body subunit c was previously found to be TML. In the present study, subunit c was isolated from the storage bodies of humans with juvenile ceroid-lipofuscinosis, and from sheep and mice with apparently analogous diseases. In all three species, partial amino acid sequence analysis of the stored subunit c indicated that the protein contained TML at residue 43. These findings strongly suggest that specific methylation of lysine residue 43 of mitochondrial ATP synthase plays a central role in the lysosomal storage of this protein.