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A Feed-Forward Circuit of EndogenousPGC-1αandEstrogen Related Receptor αRegulates the Neuronal Electron Transport Chain

Authors :
Zhixiang Liao
Clemens R. Scherzer
Rachit Bakshi
Shuchi Mittal
Source :
Parkinson's Disease, Parkinson's Disease, Vol 2016 (2016)
Publication Year :
2016
Publisher :
Hindawi Limited, 2016.

Abstract

Peroxisome proliferator-activated receptor γcoactivator 1α(PGC-1α) is a central regulator of cellular and mitochondrial metabolism. Cellular bioenergetics are critically important in “energy-guzzling” neurons, but the components and wiring of the transcriptional circuit through whichPGC-1αregulates the neuronal electron transport chain have not been established. This information may be vital for restoring neuronal bioenergetics gene expression that is compromised during incipient Parkinson’s neuropathology and in aging-dependent brain diseases. Here we delineate a neuronal transcriptional circuit controlled by endogenousPGC-1α. We show that a feed-forward circuit of endogenous neuronalPGC-1αand the orphan nuclear estrogen-related receptorα(ERRα) activates the nuclear-encoded mitochondrial electron transport chain.PGC-1αnot onlytrans-activated expression ofERRα, but also coactivatedERRαtarget genes in complexes I, II, IV, and V of the neuronal electron transport chain via association with evolutionary conservedERRαpromoter binding motifs. Chemical activation of this transcriptional program induced transcription of the neuronal electron transport chain. These data highlight a neuronal transcriptional circuit regulated byPGC-1αthat can be therapeutically targeted for Parkinson’s and other neurodegenerative diseases.

Details

ISSN :
20420080 and 20908083
Volume :
2016
Database :
OpenAIRE
Journal :
Parkinson's Disease
Accession number :
edsair.doi.dedup.....e92b43e0ef3f513b538fb57eda169971
Full Text :
https://doi.org/10.1155/2016/2405176