Alpha-synuclein expression in HEK293 cells enhances the mitochondrial sensitivity to rotenone.
Mitochondrial dysfunction has been implicated in the aetiology of sporadic Parkinson's disease but its role in the disease mechanism is not clear. We have investigated the short term effect of G209A mutant or wild-type alpha-synuclein expression upon mitochondrial function using stable inducible cell models. Mitochondrial respiratory chain activities and membrane potential were normal suggesting that increased wild-type or mutant alpha-synuclein expression did not directly affect these parameters. However, both wild-type and mutant G209A alpha-synuclein expression enhanced the fall in mitochondrial membrane potential induced by the complex I inhibitor rotenone. This suggests an indirect interaction between alpha-synuclein expression and mitochondrial function which could render the mitochondria more vulnerable to inhibition by potential endogenous or exogenous factors found in dopaminergic neurones.
Orth
M
M
University Department of Clinical Neuroscience, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, UK. m.orth@rfc.ucl.ac.uk
Tabrizi
S J
SJ
Schapira
A H V
AH
Cooper
J M
JM
D002460:Cell Line; D002470:Cell Survival; D002950:Citrate (si)-Synthase / Q000378:metabolism; D004579:Electron Transport; D042967:Electron Transport Complex I; D006801:Humans; D008564:Membrane Potentials; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D012402:Rotenone / Q000494:pharmacology*; D013384:Succinate Cytochrome c Oxidoreductase / Q000378:metabolism; D051843:Synucleins; D051844:alpha-Synuclein
D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein; D012402:Rotenone; D013384:Succinate Cytochrome c Oxidoreductase; D009247:NADH, NADPH Oxidoreductases; D002950:Citrate (si)-Synthase; D042967:Electron Transport Complex I