Cited by 187Adipose Tissue and MetabolismMitochondrial Function and PathologyMetabolism, Diabetes, and Cancer

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Transcriptional Control of Mitochondrial Energy Metabolism through the PGC1 Coactivators

Spiegelman, Bruce M.·2007·Novartis Foundation Symposia

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Abstract

The PGC1 transcriptional coactivators are major regulators of several crucial aspects of energy metabolism. PGC1alpha 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. ERRalpha, 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 PGC1alpha and beta 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 PGC1alpha are hypersensitive to death from oxidative stress caused by H2O2 or paraquat. Mice deficient in PGC1alpha 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.

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Authors: Spiegelman, B. M.
Affiliations: Harvard University (US)
Corresponding author: Spiegelman, Bruce M.
ORCID: Spiegelman, Bruce M.
Venue: Novartis Foundation Symposia
Publisher: Wiley
Published: 2007-10-05
Volume: 287
Pages: 60-69
ISSN: 1528-2511 (ISSN-L)
1935-4657
DOI: 10.1002/9780470725207.ch5
OpenAlex: W1589792898
Cited by: 187
References: 0
Citations by year: 2026: 1 · 2025: 3 · 2024: 7 · 2023: 8 · 2022: 7 · 2021: 11 · 2020: 8 · 2019: 13 · 2018: 11 · 2017: 11 · 2016: 7 · 2015: 16 · 2014: 14 · 2013: 14 · 2012: 17
Type: other
Language: en
Open access: closed
Licence: doi.wiley.com/10.1002/tdm_license_1.1 (tdm)
Locations: Novartis Foundation symposium (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords: PGC-1α, PGC-1β, mitochondrial bioenergetics, mitochondrial biogenesis, oxidative stress, reactive oxygen species, reactive oxygen species scavenging, nuclear receptors, estrogen-related receptor alpha, NRF1, Nrf2, catalase, glutathione peroxidase 1, manganese superoxide dismutase, oxidative stress-induced cell death, neurodegeneration, Parkinson's disease, MPTP, kainic acid-induced seizures, diabetes mellitus
MeSH terms: Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Animals, Energy Metabolism, Humans, Mitochondria, Transcription Factors, Transcription, Genetic, Trans-Activators, Reactive Oxygen Species, Oxidative Stress, Neurodegenerative Diseases

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Transcriptional Control of Mitochondrial Energy Metabolism through the PGC1 Coactivators

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