| First Author | Loeb V | Year | 2010 |
| Journal | J Biol Chem | Volume | 285 |
| Issue | 10 | Pages | 7334-43 |
| PubMed ID | 20053987 | Mgi Jnum | J:160720 |
| Mgi Id | MGI:4454977 | Doi | 10.1074/jbc.M109.061051 |
| Citation | Loeb V, et al. (2010) The transgenic overexpression of alpha-synuclein and not its related pathology associates with complex I inhibition. J Biol Chem 285(10):7334-43 |
| abstractText | Alpha-synuclein (alphaS) is a protein involved in the cytopathology and genetics of Parkinson disease and is thought to affect mitochondrial complex I activity. Previous studies have shown that mitochondrial toxins and specifically inhibitors of complex I activity enhance alphaS pathogenesis. Here we show that alphaS overexpression specifically inhibits complex I activity in dopaminergic cells and in A53T alphaS transgenic mouse brains. Importantly, our results indicate that the inhibitory effect on complex I activity is not associated with alphaS-related pathology. Specifically, complex I activity measured in purified mitochondria from A53T alphaS transgenic mouse brains was not affected by mouse age; Parkinson disease-like symptoms; levels of alphaS soluble oligomers; levels of insoluble, lipid-associated alphaS; or alphaS intraneuronal depositions in vivo. Likewise, no correlation was found between complex I activity and polyunsaturated fatty acid-induced alphaS depositions in Lewy body-like inclusions in cultured dopaminergic cells. We further show that the effect of alphaS on complex I activity is not due to altered mitochondrial protein levels or affected complex I assembly. Based on the results herein, we suggest that alphaS expression negatively regulates complex I activity as part of its normal, physiological role. |
