RGD Reference Report - Early Expression of Parkinson's Disease-Related Mitochondrial Abnormalities in PINK1 Knockout Rats. - Rat Genome Database

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Early Expression of Parkinson's Disease-Related Mitochondrial Abnormalities in PINK1 Knockout Rats.

Authors: Villeneuve, LM  Purnell, PR  Boska, MD  Fox, HS 
Citation: Villeneuve LM, etal., Mol Neurobiol. 2016 Jan;53(1):171-86. doi: 10.1007/s12035-014-8927-y. Epub 2014 Nov 25.
RGD ID: 11560775
Pubmed: PMID:25421206   (View Abstract at PubMed)
PMCID: PMC4442772   (View Article at PubMed Central)
DOI: DOI:10.1007/s12035-014-8927-y   (Journal Full-text)

PTEN-induced kinase 1 (PINK1) mutations are responsible for an autosomal recessive, familial form of Parkinson's disease. PINK1 protein is a Ser/Thr kinase localized to the mitochondrial membrane and is involved in many processes including mitochondrial trafficking, mitophagy, and proteasomal function. Using a new PINK1 knockout (PINK1 KO) rat model, we found altered brain metabolomic markers using magnetic resonance spectroscopy, identified changes in mitochondrial pathways with quantitative proteomics using sequential window acquisition of all theoretical spectra (SWATH) mass spectrometry, and demonstrated mitochondrial functional alterations through measurement of oxygen consumption and acidification rates. The observed alterations included reduced creatine, decreased levels of complex I of the electron transport chain, and increased proton leak in the electron transport chain in PINK1 KO rat brains. In conjunction, these results demonstrate metabolomic and mitochondrial alterations occur during the asymptomatic phase of Parkinson's disease in this model. These results indicate both potential early diagnostic markers and therapeutic pathways that can be used in PD.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Parkinson's disease  IMP 11560775; 11560775; 11560775 RGD 
Parkinson's disease  ISOPink1 (Rattus norvegicus)11560775; 11560775 RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
mitochondrial fission  HMP 11560775 RGD 
negative regulation of fatty acid beta-oxidation  HMP 11560775 RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
decreased substantia nigra cell number  IMP 11560775; 11560775; 11560775compared to LEHRGD 
decreased substantia nigra size  IMP 11560775; 11560775; 11560775compared to LEHRGD 
increased oxygen consumption onsetIMP 11560775; 11560775; 11560775compared to LEHRGD 
Objects Annotated

Genes (Rattus norvegicus)
Pink1  (PTEN induced kinase 1)
Pink1em1Sage  (PTEN induced putative kinase 1; zinc finger nuclease induced mutant 1, Sigma Advanced Genetic Engineering Labs)

Genes (Mus musculus)
Pink1  (PTEN induced putative kinase 1)

Genes (Homo sapiens)
PINK1  (PTEN induced kinase 1)

Strains
LE-Pink1em1Sage-/-  (NA)


Additional Information