PMID- 18245779
OWN - NLM
STAT- MEDLINE
DCOM- 20080623
LR  - 20190327
IS  - 1460-2083 (Electronic)
IS  - 0964-6906 (Linking)
VI  - 17
IP  - 10
DP  - 2008 May 15
TI  - Deficiency of the INCL protein Ppt1 results in changes in ectopic F1-ATP synthase 
      and altered cholesterol metabolism.
PG  - 1406-17
LID - 10.1093/hmg/ddn028 [doi]
AB  - Infantile neuronal ceroid lipofuscinosis (INCL) is a severe neurodegenerative 
      disease caused by deficiency of palmitoyl protein thioesterase 1 (PPT1). INCL 
      results in dramatic loss of thalamocortical neurons, but the disease mechanism 
      has remained elusive. In the present work we describe the first interaction 
      partner of PPT1, the F(1)-complex of the mitochondrial ATP synthase, by 
      co-purification and in vitro-binding assays. In addition to mitochondria, 
      subunits of F(1)-complex have been reported to localize in the plasma membrane, 
      and to be capable of acting as receptors for various ligands such as 
      apolipoprotein A-1. We verified here the plasma membrane localization of 
      F(1)-subunits on mouse primary neurons and fibroblasts by cell surface 
      biotinylation and TIRF-microscopy. To gain further insight into the Ppt1-mediated 
      properties of the F(1)-complex, we utilized the Ppt1-deficient Ppt1(Delta ex4) 
      mice. While no changes in the mitochondrial function could be detected in the 
      brain of the Ppt1(Delta ex4) mice, the levels of F(1)-subunits alpha and beta on 
      the plasma membrane were specifically increased in the Ppt1(Delta ex4) neurons. 
      Significant changes were also detected in the apolipoprotein A-I uptake by the 
      Ppt1(Delta ex4) neurons and the serum lipid composition in the Ppt1(Delta ex4) 
      mice. These data indicate neuron-specific changes for F(1)-complex in the 
      Ppt1-deficient cells and give clues for a possible link between lipid metabolism 
      and neurodegeneration in INCL.
FAU - Lyly, Annina
AU  - Lyly A
AD  - National Public Health Institute and FIMM, Institute for Molecular Medicine, 
      Biomedicum Helsinki, PO Box 104, FIN-00251 Helsinki, Finland.
FAU - Marjavaara, Sanna K
AU  - Marjavaara SK
FAU - Kyttala, Aija
AU  - Kyttala A
FAU - Uusi-Rauva, Kristiina
AU  - Uusi-Rauva K
FAU - Luiro, Kaisu
AU  - Luiro K
FAU - Kopra, Outi
AU  - Kopra O
FAU - Martinez, Laurent O
AU  - Martinez LO
FAU - Tanhuanpaa, Kimmo
AU  - Tanhuanpaa K
FAU - Kalkkinen, Nisse
AU  - Kalkkinen N
FAU - Suomalainen, Anu
AU  - Suomalainen A
FAU - Jauhiainen, Matti
AU  - Jauhiainen M
FAU - Jalanko, Anu
AU  - Jalanko A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080201
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (Apolipoprotein A-I)
RN  - 0 (Lipids)
RN  - 0 (Protein Subunits)
RN  - 0 (respiratory complex II)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 1.3.5.1 (Electron Transport Complex II)
RN  - EC 3.1.2.- (Thiolester Hydrolases)
RN  - EC 3.1.2.22 (palmitoyl-protein thioesterase)
RN  - EC 3.6.3.14 (Proton-Translocating ATPases)
SB  - IM
MH  - Animals
MH  - Apolipoprotein A-I/blood/metabolism
MH  - Brain/abnormalities/metabolism/pathology/physiopathology
MH  - Cell Membrane/metabolism
MH  - Cholesterol/blood/*metabolism
MH  - Electron Transport Complex II/metabolism
MH  - Female
MH  - Humans
MH  - Lipid Metabolism
MH  - Lipids/blood
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mitochondria/enzymology/metabolism
MH  - Neuroglia/metabolism
MH  - Neuronal Ceroid-Lipofuscinoses/*metabolism
MH  - Neurons/cytology/metabolism
MH  - Protein Subunits/analysis/metabolism
MH  - Proton-Translocating ATPases/analysis/*metabolism
MH  - Thiolester Hydrolases/blood/*genetics/isolation & purification/*metabolism
EDAT- 2008/02/05 09:00
MHDA- 2008/06/24 09:00
CRDT- 2008/02/05 09:00
PHST- 2008/02/05 09:00 [pubmed]
PHST- 2008/06/24 09:00 [medline]
PHST- 2008/02/05 09:00 [entrez]
AID - ddn028 [pii]
AID - 10.1093/hmg/ddn028 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2008 May 15;17(10):1406-17. doi: 10.1093/hmg/ddn028. Epub 2008 Feb 
      1.