RGD Reference Report - Potential roles of PINK1 for increased PGC-1alpha-mediated mitochondrial fatty acid oxidation and their associations with Alzheimer disease and diabetes. - Rat Genome Database

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Potential roles of PINK1 for increased PGC-1alpha-mediated mitochondrial fatty acid oxidation and their associations with Alzheimer disease and diabetes.

Authors: Choi, J  Ravipati, A  Nimmagadda, V  Schubert, M  Castellani, RJ  Russell, JW 
Citation: Choi J, etal., Mitochondrion. 2014 Sep;18:41-8. doi: 10.1016/j.mito.2014.09.005. Epub 2014 Sep 23.
RGD ID: 10047114
Pubmed: PMID:25260493   (View Abstract at PubMed)
PMCID: PMC4911223   (View Article at PubMed Central)
DOI: DOI:10.1016/j.mito.2014.09.005   (Journal Full-text)

Down-regulation of PINK1 and PGC-1alpha proteins is implicated in both mitochondrial dysfunction and oxidative stress potentially linking metabolic abnormality and neurodegeneration. Here, we report that PGC-1alpha and PINK1 expression is markedly decreased in Alzheimer disease (AD) and diabetic brains. We observed a significant down-regulation of PGC-1alpha and PINK1 protein expression in H2O2-treated cells but not in those cells treated with N-acetyl cysteine. The protein levels of two key enzymes of the mitochondrial beta-oxidation machinery, acyl-coenzyme A dehydrogenase, very long chain (ACADVL) and mitochondrial trifunctional enzyme subunit alpha are significantly decreased in AD and diabetic brains. Moreover, we observed a positive relationship between ACADVL and 64 kDa PINK1 protein levels in AD and diabetic brains. Overexpression of PGC-1alpha decreases lipid-droplet accumulation and increases mitochondrial fatty acid oxidation; down-regulation of PINK1 abolishes these effects. Together, these results provide new insights into potential cooperative roles of PINK1 and PGC-1alpha in mitochondrial fatty acid oxidation, suggesting possible regulatory roles for mitochondrial function in the pathogenesis of AD and diabetes.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Alzheimer's disease  IEP 10047114; 10047114protein:decreased expression:brainRGD 
Alzheimer's disease  ISOACADVL (Homo sapiens)10047114; 10047114protein:decreased expression:brainRGD 
Alzheimer's disease  ISOHADHA (Homo sapiens)10047114; 10047114protein:decreased expression:brainRGD 
Experimental Diabetes Mellitus  ISOAcadvl (Mus musculus)10047114; 10047114protein:decreased expression:brainRGD 
Experimental Diabetes Mellitus  IEP 10047114; 10047114protein:decreased expression:brainRGD 
Experimental Diabetes Mellitus  ISOHadha (Mus musculus)10047114; 10047114protein:decreased expression:brainRGD 

Objects Annotated

Genes (Rattus norvegicus)
Acadvl  (acyl-CoA dehydrogenase, very long chain)
Hadha  (hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha)

Genes (Mus musculus)
Acadvl  (acyl-Coenzyme A dehydrogenase, very long chain)
Hadha  (hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha)

Genes (Homo sapiens)
ACADVL  (acyl-CoA dehydrogenase very long chain)
HADHA  (hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha)


Additional Information