Mitochondrial ATP synthase subunit c stored in hereditary ceroid-lipofuscinosis contains trimethyl-lysine.
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.
Katz
M L
ML
Mason Eye Institute, University of Missouri, Columbia 65212, USA.
Gao
C L
CL
Tompkins
J A
JA
Bronson
R T
RT
Chin
D T
DT
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001344:Autopsy; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D003594:Cytoplasmic Granules / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives* / Q000032:analysis; D046911:Macromolecular Substances; D051379:Mice; D008928:Mitochondria / Q000201:enzymology*; D008969:Molecular Sequence Data; D009472:Neuronal Ceroid-Lipofuscinoses / Q000201:enzymology* / Q000235:genetics* / Q000662:veterinary; D006180:Proton-Translocating ATPases / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D012376:Rodent Diseases; D012756:Sheep; D012757:Sheep Diseases
D046911:Macromolecular Substances; C003712:trimethyllysine; D006180:Proton-Translocating ATPases; D008239:Lysine