ArticleJournal of neurochemistry2013
Neuron-specific specificity protein 4 bigenomically regulates the transcription of all mitochondria- and nucleus-encoded cytochrome c oxidase subunit genes in neurons.
Article in Journal of neurochemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- Bioinformatics analysis of comorbid mechanisms between ischemic stroke and end stage renal disease.Scientific reports · 2025Article
- Peripheral Neuroinflammation and Pain: How Acute Pain Becomes Chronic.Current neuropharmacology · 2024Review
- Mapping chromatin accessibility and active regulatory elements reveals pathological mechanisms in human gliomas.Nature communications · 2021Article
- miR-181c Activates Mitochondrial Calcium Uptake by Regulating MICU1 in the Heart.Journal of the American Heart Association · 2019Article
- Article
- CytochromeFrontiers in physiology · 2019Review
- Neuronal Apolipoprotein E4 Expression Results in Proteome-Wide Alterations and Compromises Bioenergetic Capacity by Disrupting Mitochondrial Function.Journal of Alzheimer's disease : JAD · 2019Article
- Podocyte-Specific Loss of Krüppel-Like Factor 6 Increases Mitochondrial Injury in Diabetic Kidney Disease.Diabetes · 2018Article
- p38/Sp1/Sp4/HDAC4/BDNF Axis Is a Novel Molecular Pathway of the Neurotoxic Effect of the Methylmercury.Frontiers in neuroscience · 2017Article
- Specificity protein 4 (Sp4) transcriptionally regulates inhibitory GABAergic receptors in neurons.Biochimica et biophysica acta · 2016Article
- Mitochondria-related miR-141-3p contributes to mitochondrial dysfunction in HFD-induced obesity by inhibiting PTEN.Scientific reports · 2015Article
- Transcriptome analysis of complex I-deficient patients reveals distinct expression programs for subunits and assembly factors of the oxidative phosphorylation system.BMC genomics · 2015Article
- Krüppel-like factor 6 regulates mitochondrial function in the kidney.The Journal of clinical investigation · 2015Article
- Nuclear respiratory factor 2 regulates the transcription of AMPA receptor subunit GluA2 (Gria2).Biochimica et biophysica acta · 2014Article
- Echinochrome a increases mitochondrial mass and function by modulating mitochondrial biogenesis regulatory genes.Marine drugs · 2014Article
- Store-operated calcium entry promotes the degradation of the transcription factor Sp4 in resting neurons.Science signaling · 2014Article
- Brain Na(+), K(+)-ATPase Activity In Aging and Disease.International journal of biomedical science : IJBS · 2014Article
- Regulation of Na(+)/K(+)-ATPase by neuron-specific transcription factor Sp4: implication in the tight coupling of energy production, neuronal activity and energy consumption in neurons.The European journal of neuroscience · 2014Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Neurons are highly dependent on oxidative metabolism for their energy supply, and cytochrome c oxidase (COX) is a key energy-generating enzyme in the mitochondria. A unique feature of COX is that it is one of only four proteins in mammalian cells that are bigenomically regulated. Of its thirteen subunits, three are encoded in the mitochondrial genome and ten are nuclear-encoded on nine different chromosomes. The mechanism of regulating this multisubunit, bigenomic enzyme poses a distinct challenge. In recent years, we found that nuclear respiratory factors 1 and 2 (NRF-1 and NRF-2) mediate such bigenomic coordination. The latest candidate is the specificity factor (Sp) family of proteins. In N2a cells, we found that Sp1 regulates all 13 COX subunits. However, we discovered recently that in primary neurons, it is Sp4 and not Sp1 that regulates some of the key glutamatergic receptor subunit genes. The question naturally arises as to the role of Sp4 in regulating COX in primary neurons. The present study utilized multiple approaches, including chromatin immunoprecipitation, promoter mutational analysis, knockdown and over-expression of Sp4, as well as functional assays to document that Sp4 indeed functionally regulate all 13 subunits of COX as well as mitochondrial transcription factors A and B. The present study discovered that among the specificity family of transcription factors, it is the less known neuron-specific Sp4 that regulates the expression of all 13 subunits of mitochondrial cytochrome c oxidase (COX) enzyme in primary neurons. Sp4 also regulates the three mitochondrial transcription factors (TFAM, TFB1M, and TFB2M) and a COX assembly protein SURF-1 in primary neurons.
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Registered trials
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