PGC-1α: a master gene that is hard to master

Cell Mol Life Sci. 2012 Aug;69(15):2465-8. doi: 10.1007/s00018-012-1043-0. Epub 2012 Jun 9.

Abstract

Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a transcriptional coactivator that favorably affects mitochondrial function. This concept is supported by an increasing amount of data including studies in PGC-1α gene-deleted mice, suggesting that PGC-1α is a rescue factor capable of boosting cell metabolism and promoting cell survival. However, this view has now been called into question by a recent study showing that adeno-associated virus-mediated PGC-1α overexpression causes overt cell degeneration in dopaminergic neurons. How is this to be understood, and can these seemingly conflicting findings tell us something about the role of PGC-1α in cell stress and in control of neuronal homeostasis?

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Dopaminergic Neurons / physiology
  • Heat-Shock Proteins / genetics*
  • Heat-Shock Proteins / physiology*
  • Homeostasis
  • Humans
  • Mice
  • Mice, Knockout
  • Mitochondria / physiology
  • Models, Neurological
  • Nerve Degeneration / genetics
  • Nerve Degeneration / physiopathology
  • Parkinson Disease / etiology
  • Parkinson Disease / genetics
  • Parkinson Disease / physiopathology
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / physiology
  • Trans-Activators / deficiency
  • Trans-Activators / genetics*
  • Trans-Activators / physiology*
  • Transcription Factors / genetics*
  • Transcription Factors / physiology*

Substances

  • Heat-Shock Proteins
  • PPARGC1A protein, human
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, mouse
  • Ppargc1a protein, rat
  • RNA-Binding Proteins
  • Trans-Activators
  • Transcription Factors