Transcriptional regulatory circuits controlling mitochondrial biogenesis and function

Kelly, Daniel P.; Scarpulla, Richard C.

doi:10.1101/gad.1177604

Cited by 1,243Mitochondrial Function and PathologyAdipose Tissue and MetabolismAutophagy in Disease and Therapy

Transcriptional regulatory circuits controlling mitochondrial biogenesis and function

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Kelly, Daniel P., Scarpulla, Richard C.·2004·Genes & Development

DOI 10.1101/gad.1177604

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Abstract

We are witnessing a period of renewed interest in the biology of the mitochondrion. The mitochondrion serves a critical function in the maintenance of cellular energy stores, thermogenesis, and apoptosis. Moreover, alterations in mitochondrial function contribute to several inherited and acquired human diseases and the aging process. This review summarizes our understanding of the transcriptional regulatory mechanisms involved in the biogenesis and energy metabolic function of mitochondria in higher organisms.

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Mitochondrial biogenesis requires activation of a number of transcription factors in addition to PPARδ.
“It is well established that the biogenesis of normal, functional mitochondria requires the activation of a number of transcription factors in addition to PPARδ (22–24).”
From High-fat diets cause insulin resistance despite an increase in muscle mitochondria (2008) · cites this paper as [22]
PGC-1α mediates the coordinated increase in transcription of genes encoding mitochondrial proteins and plays the key role in adaptive mitochondrial biogenesis.
“The coordinated increase in transcription of genes encoding mitochondrial proteins is mediated by the transcription coactivator PGC-1α, which activates the NRFs, ERRs, PPARs, and MEFs and, thus, plays the key role in mediating adaptive mitochondrial biogenesis (22–24).”
From High-fat diets cause insulin resistance despite an increase in muscle mitochondria (2008) · cites this paper as [22]
Chronic exposure to relatively high levels of NO results in mitochondrial biogenesis, which could reprogram a cell or tissue to have a higher metabolic capacity.
“Chronic exposure to relatively high levels of NO results in mitochondrial biogenesis [113-115], which could reprogram a cell or tissue to have a higher metabolic capacity.”
From Regulation of obesity and insulin resistance by nitric oxide (2014) · cites this paper as [113]

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Nuclear Transcription Factors in Cytochrome c and Cytochrome Oxidase Expression
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“All of these transcription factors directly regulate the expression of certain nuclear-encoded mitochondrial genes and were discussed in greater detail in two recent reviews (Kelly and Scarpulla, 2004; Puigserver and Spiegelman, 2003).”
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Background
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“Given the multitude of transcription factors that regulate energy metabolism genes [59] and the fact that ERRα function is context (tissue- and signal-) dependent, the apparent lack of phenotype, other than the resistance to diet-induced obesity, may not be so surprising.”
Background
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Authors: Kelly, D. P., & Scarpulla, R. C.
Affiliations: Washington University in St. Louis (US)
ORCID: Kelly, Daniel P.
Venue: Genes & Development
Publisher: Cold Spring Harbor Laboratory
Published: 2004-02-15
Volume: 18
Issue: 4
Pages: 357-368
ISSN: 0890-9369 (ISSN-L)
1549-5477
DOI: 10.1101/gad.1177604
OpenAlex: W2113515610
Cited by: 1,243
References: 108
Citations by year: 2026: 21 · 2025: 21 · 2024: 31 · 2023: 50 · 2022: 53 · 2021: 53 · 2020: 47 · 2019: 67 · 2018: 53 · 2017: 63 · 2016: 67 · 2015: 62 · 2014: 65 · 2013: 64 · 2012: 84
Type: posted content
Language: en
Open access: bronze
doi.org
Locations: Genes & Development (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5p50hl061006-05, HL57278)
U.S. Public Health Service
National Heart, Lung, and Blood Institute (P01HL057278, HL58493, HL57278, R01HL058493, HL-61006)
National Institute of General Medical Sciences (GM32525)
National Institute of Diabetes and Digestive and Kidney Diseases (DK 45416)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
Keywords: mitochondrial biogenesis, mitochondrial function, transcriptional regulation, transcriptional regulatory networks, mitochondrial bioenergetics, thermogenesis, apoptosis, mitochondrial disease, aging
MeSH terms: Animals, Cell Nucleus, DNA, Mitochondrial, Enzymes, Gene Expression Regulation, Humans, Mitochondria, Transcription, Genetic, Vertebrates, Genome

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Transcriptional regulatory circuits controlling mitochondrial biogenesis and function

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