title: Lysosomal Storage of Subunit c of Mitochondrial ATP Synthase in Brain-Specific Atp13a2-Deficient Mice.
abstract: Kufor-Rakeb syndrome (KRS) is an autosomal recessive form of early-onset parkinsonism linked to the PARK9 locus. The causative gene for KRS is Atp13a2, which encodes a lysosomal type 5 P-type ATPase. We recently showed that KRS/PARK9-linked mutations lead to several lysosomal alterations, including reduced proteolytic processing of cathepsin D in vitro. However, it remains unknown how deficiency of Atp13a2 is connected to lysosomal impairments. To address this issue, we analyzed brain tissues of Atp13a2 conditional-knockout mice, which exhibited characteristic features of neuronal ceroid lipofuscinosis, including accumulation of lipofuscin positive for subunit c of mitochondrial ATP synthase, suggesting that a common pathogenic mechanism underlies both neuronal ceroid lipofuscinosis and Parkinson disease.
authors: Department of Neurology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors: Shigeto
authors: S
authors: Sato
authors: Department of Cell Biology and Neuroscience, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors: Masato
authors: M
authors: Koike
authors: Research Institute for Disease of Old Age, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors: Manabu
authors: M
authors: Funayama
authors: Translational Research Center, Fukushima Medical University, Fukushima, Japan.
authors: Junji
authors: J
authors: Ezaki
authors: Division of Neuropathology, Department of Neuropathology, The Jikei University School of Medicine, Tokyo, Japan.
authors: Takahiro
authors: T
authors: Fukuda
authors: Laboratory of Proteomics and Biomolecular, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors: Takashi
authors: T
authors: Ueno
authors: Department of Cellular and Molecular Neuropathology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors: Yasuo
authors: Y
authors: Uchiyama
authors: Department of Neurology, Juntendo University Graduate School of Medicine, Tokyo, Japan. Electronic address: nhattori@juntendo.ac.jp.
authors: Nobutaka
authors: N
authors: Hattori
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000201:enzymology / Q000473:pathology; D002402:Cathepsin D / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D055786:Gene Knockout Techniques; D006801:Humans; D008062:Lipofuscin / Q000378:metabolism; D008247:Lysosomes / Q000201:enzymology / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009472:Neuronal Ceroid-Lipofuscinoses / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D009928:Organ Specificity; D010300:Parkinson Disease / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D020734:Parkinsonian Disorders / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D006180:Proton-Translocating ATPases / Q000235:genetics* / Q000378:metabolism
chemical_list: C514983:ATP13A2 protein, human; D008062:Lipofuscin; D008565:Membrane Proteins; D002402:Cathepsin D; C572751:ATP13A2 protein, mouse; D000251:Adenosine Triphosphatases; C103607:mitochondrial ATPase subunit c; D025261:Mitochondrial Proton-Translocating ATPases; D006180:Proton-Translocating ATPases