GABP Transcription Factor (Nuclear Respiratory Factor 2) Is Required for Mitochondrial Biogenesis

Yang, Zhong-Fa; Drumea, Karen; Mott, Stephanie; Wang, Junling; Rosmarin, Alan G.

doi:10.1128/mcb.00492-12

Cited by 112Mitochondrial Function and PathologyAdipose Tissue and MetabolismAutophagy in Disease and Therapy

GABP Transcription Factor (Nuclear Respiratory Factor 2) Is Required for Mitochondrial Biogenesis

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Yang, Zhong-Fa, Drumea, Karen, Mott, Stephanie, Wang, Junling, Rosmarin, Alan G.·2014·Molecular and Cellular Biology

DOI 10.1128/mcb.00492-12PMC PMC4135556

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Abstract

Mitochondria are membrane-bound cytoplasmic organelles that serve as the major source of ATP production in eukaryotic cells. GABP (also known as nuclear respiratory factor 2) is a nuclear E26 transformation-specific transcription factor (ETS) that binds and activates mitochondrial genes that are required for electron transport and oxidative phosphorylation. We conditionally deleted Gabpa, the DNA-binding component of this transcription factor complex, from mouse embryonic fibroblasts (MEFs) to examine the role of Gabp in mitochondrial biogenesis, function, and gene expression. Gabpα loss modestly reduced mitochondrial mass, ATP production, oxygen consumption, and mitochondrial protein synthesis but did not alter mitochondrial morphology, membrane potential, apoptosis, or the expression of several genes that were previously reported to be GABP targets. However, the expression of Tfb1m, a methyltransferase that modifies ribosomal rRNA and is required for mitochondrial protein translation, was markedly reduced in Gabpα-null MEFs. We conclude that Gabp regulates Tfb1m expression and plays an essential, nonredundant role in mitochondrial biogenesis.

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These factors, including nuclear respiratory factor 1, nuclear factor erythroid-2-like 2, GA binding protein (nuclear respiratory factor 2), and Sp4, directly and indirectly control the expression of respiratory chain subunits encoded by nuclear and mitochondrial DNA.
“These factors, including nuclear respiratory factor 1, nuclear factor erythroid-2-like 2, GA binding protein (nuclear respiratory factor 2), and Sp4 [110–114] directly and indirectly control the expression of respiratory chain subunits encoded by nuclear and mitochondrial DNA [110, 115, 116].”
From Neuronal Apolipoprotein E4 Expression Results in Proteome-Wide Alterations and Compromises Bioenergetic Capacity by Disrupting Mitochondrial Function (2019) · cites this paper as [112]

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Mitochondrial transcription factors B1 and B2 activate transcription of human mtDNA
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“(Invitrogen) at 5 g/ml at 37°C for 30 to 60 min (19), followed by flow”
Background
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Authors: Yang, Z.-F., Drumea, K., Mott, S., Wang, J., & Rosmarin, A. G.
Affiliations: University of Massachusetts Medical School, Worcester, Massachusetts, USA
Rambam Health Care Campus (IL)
Brown University (US)
University of Massachusetts Chan Medical School (US)
ORCID: Wang, Junling
Venue: Molecular and Cellular Biology
Publisher: Informa UK Limited
Published: 2014-09-01
Volume: 34
Issue: 17
Pages: 3194-3201
ISSN: 0270-7306 (ISSN-L)
1098-5549
DOI: 10.1128/mcb.00492-12
PMC: PMC4135556
OpenAlex: W1993560895
Cited by: 112
References: 4
Citations by year: 2026: 9 · 2025: 7 · 2024: 11 · 2023: 5 · 2022: 15 · 2021: 10 · 2020: 12 · 2019: 11 · 2018: 12 · 2017: 11 · 2016: 4 · 2015: 5
FWCI: 2.52
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Molecular and Cellular Biology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Heart, Lung, and Blood Institute (R01HL073945)
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: GABP, GABPA, mitochondrial biogenesis, ETS transcription factors, TFB1M, mitochondrial translation, mitochondrial gene expression, ATP production, mouse embryonic fibroblasts, conditional gene deletion
MeSH terms: Adenosine Triphosphate, Animals, Cells, Cultured, Fibroblasts, Gene Expression Regulation, Mitochondria, Oxygen Consumption, RNA, Ribosomal, Transcription Factors, Apoptosis, Mice, Knockout, Genes, Mitochondrial, GA-Binding Protein Transcription Factor, Mice, Membrane Potential, Mitochondrial

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GABP Transcription Factor (Nuclear Respiratory Factor 2) Is Required for Mitochondrial Biogenesis

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