Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8399291 | Mitochondrion | 2014 | 8 Pages |
Abstract
Down-regulation of PINK1 and PGC-1α proteins is implicated in both mitochondrial dysfunction and oxidative stress potentially linking metabolic abnormality and neurodegeneration. Here, we report that PGC-1α and PINK1 expression is markedly decreased in Alzheimer disease (AD) and diabetic brains. We observed a significant down-regulation of PGC-1α 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 β-oxidation machinery, acyl-coenzyme A dehydrogenase, very long chain (ACADVL) and mitochondrial trifunctional enzyme subunit α 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-1α 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-1α in mitochondrial fatty acid oxidation, suggesting possible regulatory roles for mitochondrial function in the pathogenesis of AD and diabetes.
Keywords
PBSACADVLOCRCPT-1PGC-1αSTZPINK1PMSFTCAHEKDMEMDulbecco's modified Eagle's mediumPTEN-induced putative kinase 1streptozotocinamyotrophic lateral sclerosisAlzheimer diseaseALSDiabetesHuntington diseaseParkinson diseaseHADHAhuman embryonic kidney cellsPhosphate buffered salinephenylmethylsulfonyl fluorideMitochondriaOxygen consumption rate
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Authors
Joungil Choi, Avinash Ravipati, Vamshi Nimmagadda, Manfred Schubert, Rudolph J. Castellani, James W. Russell,