Transcriptional Control of Mitochondrial Energy Metabolism through the PGC1 Coactivators

  1. Derek J. Chadwick Organizer and
  2. Jamie Goode
  1. Bruce M. Spiegelman

Published Online: 20 MAY 2008

DOI: 10.1002/9780470725207.ch5

Mitochondrial Biology: New Perspectives: Novartis Foundation Symposium 287

Mitochondrial Biology: New Perspectives: Novartis Foundation Symposium 287

How to Cite

Spiegelman, B. M. (2007) Transcriptional Control of Mitochondrial Energy Metabolism through the PGC1 Coactivators, in Mitochondrial Biology: New Perspectives: Novartis Foundation Symposium 287 (eds D. J. Chadwick and J. Goode), John Wiley & Sons, Ltd, Chichester, UK. doi: 10.1002/9780470725207.ch5

Author Information

  1. Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA

Publication History

  1. Published Online: 20 MAY 2008
  2. Published Print: 5 OCT 2007

Book Series:

  1. Novartis Foundation Symposia

Book Series Editors:

  1. Novartis Foundation

ISBN Information

Print ISBN: 9780470066577

Online ISBN: 9780470725207

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Keywords:

  • mitochondrial dysfunction and neurodegeneration;
  • electron transport system function;
  • motor nerve activity;
  • reactive oxygen species metabolism;
  • muscle wasting and dystrophies

Summary

The PGC1 transcriptional coactivators are major regulators of several crucial aspects of energy metabolism. PGC1α controls many aspects of oxidative metabolism, including mitochondrial biogenesis and respiration through the coactivation of many nuclear receptors, and factors outside the nuclear receptor family. ERRα, NRF1 and NRF2 are key targets of the PGC1s in mitochondrial biogenesis. We have recently addressed the question of the role of PGC1 coactivators in the metabolism of reactive oxygen species (ROS). We now show that PGC1α and β are induced when cells are given an oxidative stressor, H2O2. In fact, experiments with either genetic knockouts or RNAi for the PGC1s show that the ability of ROS to induce a ROS scavenging programme depends entirely on the PGC1s. This includes genes encoding mitochondrial proteins like SOD2, but also includes cytoplasmic proteins such as catalase and GPX1. Cells lacking PGC1α are hypersensitive to death from oxidative stress caused by H2O2 or paraquat. Mice deficient in PGC1α get excessive neurodegeneration when given kainic acid-induced seizures or MPTP, which causes Parkinsonism. These data show that the PGC1s are key modulators of mitochondrial biology and important protective molecules against ROS generation and damage. The implications of this for diabetes and neurodegenerative diseases are discussed.