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PGC‐1 Coactivators and the Control of Energy Homeostasis
Author(s) -
Spiegelman Bruce M.,
Pierre Julie St.,
Drori Stavit,
Uldry Marc,
Lin Jiandie,
Bachoo Robert
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a455
Subject(s) - mitochondrial biogenesis , neurodegeneration , mitochondrion , microbiology and biotechnology , biology , sod2 , mitochondrial ros , reactive oxygen species , oxidative stress , ppargc1a , nuclear receptor , regulator , transcription factor , coactivator , biochemistry , superoxide dismutase , medicine , gene , disease
We have previously shown that the PGC‐1 transcriptional coactivators are major regulators of several crucial aspects of energy metabolism. PGC‐1αis a major regulator of many aspects of oxidative metabolism, including mitochondrial biogenesis and respiration through the coactivation of many nuclear receptors, and factors outside the nuclear receptor family. We have recently addressed the question of the role of PGC‐1 coactivators in the metabolism of ROS. Since these factors are very powerful inducers of mitochondrial biogenesis and respiration, it might have been expected that they could increase ROS formation. We now show that PGC‐1α and β, are induced when cells are given an oxidative stressor, H2O2. In fact, experiments with RNAi for the PGC‐1s show that the ability of ROS to induce and ROS scavenging program depends entirely on the PGC‐1s. This includes genes encoding mitochondrial proteins like SOD2, but also includes cytoplasmic proteins like catalase. Using mice deficient in PGC‐1α, we have studied their resistance to oxidative challenges. The mice get excessive neurodegeneration when given kainic‐acid induced seizures or MPTP, which causes Parkinsonism. These data show that the PGC‐1s are important protective molecules against ROS generation and damage. The implications of this for diabetes and neurodegenerative diseases will be discussed.