FIG. 7.

Model of PGC-1α/ERRα-Sirt3 pathway in protecting against DAergic neuronal death. Extrinsic neurotoxic chemicals such as MPTP or intrinsic factors target mitochondria to stimulate ROS production at the early stage, which reduces PGC-1α expression. PGC-1α interacts with ERRα as a transcriptional coactivator and its reduction decreases Sirt3 transcription. A reduction in Sirt3 decreases the deacetylation and activation of SOD2 and ATP synthase β, resulting in ROS accumulation and ATP depletion. Increased ROS and reduced ATP affect a variety of metabolic activities, resulting in DAergic neuronal loss. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/ars