The transcriptional coactivator PGC-1alpha plays a central role in lipid metabolism;although its specific regulatory functions have been extensively studied, not much is known about the identity of potential interacting molecules that could act as coregulators and switch on/off its activity in response to metabolic cues. We have taken a biochemical approach followed by mass spectrometry and recently characterized a novel PGC-1alpha binding molecule that is able to enhance PGC-1alpha's transcriptional activity in vitro. We are currently performing gain-and loss-of-function experiments assessing the effects of this novel cofactor on the expression of genes regulated by PGC-1alpha and we are determining its overall effects on lipid beta-oxidation in vivo.In addition, we have screened the PGC-1alpha promoter to identify novel transcriptional pathways that turn on PGC-1alpha expression. We are currently validating the binding of these candidate factors and assessing the effects of their pharmachological activation on energy metabolism.

Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2013
Total Cost
$494,071
Indirect Cost
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