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Cited by 25Mitochondrial Function and PathologyNuclear Receptors and SignalingCoenzyme Q10 studies and effects

Neuron‐specific specificity protein 4 bigenomically regulates the transcription of all mitochondria‐ and nucleus‐encoded cytochrome c oxidase subunit genes in neurons

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Johar, Kaid, Priya, Anusha, Dhar, Shilpa, Liu, Qiuli, Wong‐Riley, Margaret T. T.·2013·Journal of Neurochemistry
DOI 10.1111/jnc.12433PMC PMC3820366
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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. image 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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  • 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 [116]

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  1. Arnold S Kadenbach B 1997 Cell respiration is controlled by ATP, an allosteric inhibitor of cytochrome-c oxidase Eur J Biochem 249 350 354 9363790
  2. Arnold S Goglia F Kadenbach B 1998 3,5-Diiodothyronine binds to subunit Va of cytochrome-c oxidase and abolishes the allosteric inhibition of respiration by ATP Eur J Biochem 252 325 330 9523704
  3. Basu A Park K Atchison ML Carter RS Avadhani NG 1993 Identification of a transcriptional initiator element in the cytochrome c oxidase subunit Vb promoter which binds to transcription factors NF-E1 (YY-1, delta) and Sp1 J Biol Chem 268 4188 4196 8382696
  4. Bender E Kadenbach B 2000 The allosteric ATP-inhibition of cytochrome c oxidase is reversible switched on by cAMP-dependent phosphorylation FEBS Lett 466 730 734 10648827
  5. Chu C Zavala K Fahimi A Lee J Xue Q Eilers H Schumacher MA 2011 Transcription factors Sp1 and Sp4 regulate TRPV1 gene expression in rat sensory neurons Mol Pain 7 44 21645329 PMC3121596
  6. Cole EG Gaston K 1997 A functional YY1 binding site is necessary and sufficient to activate Surf-1 promoter activity in response to serum growth factors Nuc Acids Res 25 3705 3711 PMC146936 9278494
  7. DeYoe EA Trusk TC Wong-Riley MTT 1995 Activity correlates of cytochrome oxidase-defined compartments in granular and supragranular layers of primary visual cortex of the macaque monkey Vis Neurosci 12 629 639 8527365
  8. Dhar SS Wong-Riley MTT 2011 The kinesin superfamily protein KIF17 is regulated by the same transcription factor (NRF-1) as its cargo NR2B in neurons Biochim Biophys Acta 1813 403 411 21172391 PMC3046323
  9. Dhar SS Ongwijitwat S Wong-Riley MTT 2008 Nuclear respiratory factor 1 regulates all ten nuclear-encoded subunits of cytochrome c oxidase in neurons J Biol Chem 283 3120 3129 18077450 PMC2669777
  10. Dhar SS Wong-Riley MTT 2009 Coupling of energy metabolism and synaptic transmission at the transcriptional level: Role of nuclear respiratory factor 1 in regulating both cytochrome c oxidase and NMDA glutamate receptor subunit genes J Neurosci 29 483 492 19144849 PMC2775551
  11. Dhar SS Ongwijitwat S Wong-Riley MTT 2009 Chromosoms conformation capture of all 13 genomic loci in the transcriptional regulation of the multi-subunit bigenomic cytochrome c oxidase in neurons J Biol Chem 284 18644 18650 19439416 PMC2707239
  12. Dhar SS Johar K Wong-Riley MT 2013 Bigenomic transcriptional regulation of all thirteen cytochrome c oxidase subunit genes by specificity protein 1 Open Biol 3 120176 23516108 PMC3718336
  13. Frank V Kadenbach B 1996 Regulation of the H+/e− stoichiometry of cytochrome c oxidase from bovine heart by intramitochondrial ATP/ADP ratios FEBS Lett 382 121 124 8612732
  14. Göllner H Bouwman P Mangold M Karis A Braun H Rohner I Del Rey A Besedovsky HO Meinhardt A van den Broek M Cutforth T Grosveld F Philipsen S Suske G 2001 Complex phenotype of mice homozygous for a null mutation in the Sp4 transcription factor gene Genes Cells 6 689 697 11532028
  15. Grossman LI Lomax MI 1997 Nuclear genes for cytochrome c oxidase Biochim Biophys Acta 1352 174 192 9199249
  16. Gunter TE Gunter KK Sheu SS Gavin CE 1994 Mitochondrial calcium transport: physiological and pathological relevance Am J Physiol 267 C313 C339 8074170
  17. Hagen G Müller S Beato M Suske G 1992 Cloning by recognition site screening of two novel GT box binding proteins: a family of Sp1 related genes Nucleic Acids Res 20 5519 5525 1454515 PMC334381
  18. Hevner RF Wong-Riley MTT 1989 Brain cytochrome oxidase: purification, antibody production and immunohistochemical/histochemical correlations in the CNS J Neurosci 9 3884 3898 2555458 PMC6569932
  19. Hevner RF Wong-Riley MTT 1993 Mitochondrial and nuclear gene expression for cytochrome oxidase subunits are disproportionately regulated by functional activity in neurons J Neurosci 13 1805 1819 8386752 PMC6576570
  20. Hüttermann M Kadenbach B Grossman LI 2001 Mammalian subunit IV isoforms of cytochrome c oxidase Gene 267 111 1213 11311561
  21. Hüttermann M Schmidt TR Grossman LI 2003 A third isoform of cytochrome c oxidase subunit VIII is present in mammals Gene 312 95 102 12909344
  22. Ishimaru N Tabuchi A Hara D Hayashi H Sugimoto T Yasuhara M Shiota J Tsuda M 2007 Regulation of neurotrophin-3 gene transcription by Sp3 and Sp4 in neurons J Neurochem 97 520 531 17059557
  23. Johar K Priya A Wong-Riley MTT 2012 Regulation of Na+/K+-ATPase by nuclear respiratory factor 1. Implication in the tight coupling of neuronal activity, energy generation, and energy consumption J Biol Chem 287 40381 40390 23048038 PMC3504753
  24. Kadenbach B Jarausch J Hartmann R Merle P 1983 Separation of mammalian cytochrome c oxidase into 13 polypeptides by a sodium dodecyl sulfate-gel electrophoretic procedure Anal Biochem 129 517 521 6303162
  25. Kadenbach B Stroh A Becker A Eckerskorn C Lottspeich F 1990 Tissue- and species-specific expression of cytochrome c oxidase isozymes in vertebrates Biochim Biophys Acta 1015 368 372 2153407
  26. Kadenbach B Hüttemann M Arnold S Lee I Bender E 2000 Mitochondrial energy metabolism is regulated via nuclear-coded subunits of cytochrome c oxidase Free Radic Biol Med 29 211 221 11035249
  27. Larsson NG Barsh GS Clayton DA 1997 Structure and chromosomal localization of the mouse mitochondrial transcription factor A gene (Tfam) Mamm Genome 8 139 140 9060414
  28. Li L Davie JR 2010 The role of Sp1 and Sp3 in normal and cancer cell biology Ann Anat 192 275 283 20810260
  29. Liang HL Wong-Riley MTT 2006 Activity-dependent regulation of nuclear respiratory factor-1, nuclear respiratory factor-2 and peroxisome proliferator-activated receptor gamma coactivator-1 in neurons NeuroReport 17 401 405 16514366
  30. Liang HL Ongwijitwat S Wong-Riley MTT 2006 Bigenomic functional regulation of all 13 cytochrome c oxidase subunit transcripts in rat neurons in vitro and in vivo Neurosci 140 177 190 16542778
  31. Liang HL Dhar SS Wong-Riley MTT 2010 p38 mitogen-activated protein kinase and calcium channels mediate signaling in depolarization-induced activation of peroxisome proliferator-activated receptor gamma coactivator-1alpha in neurons J Neurosci Res 88 640 649 19774670 PMC3710696
  32. Livak KJ Schmittgen TD 2001 Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method Methods 25 402 408 11846609
  33. Ma L Song L Radoi GE Harrison NL 2004 Transcriptional regulation of the mouse gene encoding the α-4 subunit of the GABAA receptor J Biol Chem 279 40451 40461 15265862
  34. Mao X Moerman-Herzog AM Wang W Barger SW 2006 Differential transcriptional control of the superoxide dismutase-2 kappa B element in neurons and astrocytes J Biol Chem 281 35863 35872 17023425 PMC2063448
  35. Mao X Yang SH Simpkins JW Barger SW 2007 Glutamate receptor activation evokes calpain-mediated degradation of Sp3 and Sp4, the prominent Sp-family transcription factors in neurons J Neurochem 100 1300 1314 17316402 PMC1949346
  36. Mao X Moerman-Herzog AM Chen Y Barger SW 2009 Unique aspects of transcriptional regulation in neurons – nuances in NFkappaB and Sp1-related factors J Neuroinflammation 6 16 19450264 PMC2693111
  37. Marin M Karis A Visser P Grosveld F Philipsen S 1997 Transcription factor Sp1 is essential for early embryonic development but dispensable for cell growth and differentiation Cell 89 619 628 9160753
  38. Napiwotzki J Shinzawa-Itoh K Yoshikawa S Kadenbach B 1997 ATP and ADP bind to cytochrome c oxidase and regulate its activity Biol Chem 378 1013 1021 9348111
  39. Ongwijitwat S Wong-Riley MTT 2004 Functional analysis of the rat cytochrome c oxidase subunit 6A1 promoter in primary neurons Gene 337 163 171 15276212
  40. Ongwijitwat S Wong-Riley MTT 2005 Is nuclear respiratory factor 2 a master transcriptional coordinator for all ten nuclear-encoded cytochrome c oxidase subunits in neurons? Gene 360 65 77 16126350
  41. Ongwijitwat S Liang HL Graboyes EM Wong-Riley MTT 2006 Nuclear respiratory factor 2 senses changing cellular energy demands and its silencing down-regulates cytochrome oxidase and other target gene mRNAs Gene 374 39 49 16516409
  42. Priya A Johar K Wong-Riley MTT 2013a Nuclear respiratory factor 2 regulates the expression of the same NMDA receptor subunit genes as NRF-1: Both factors act by a concurrent and parallel mechanism to couple energy metabolism and synaptic transmission Biochim Biophys Acta 1833 48 58 23085505 PMC3518722
  43. Priya A Johar K Wong-Riley MTT 2013b Specificity protein 4 functionally regulates the transcription of NMDA receptor subunits GluN1, GluN2A, and GluN2B Biochim Biophys Acta In press PMC3834217 23871830
  44. Ramos B Valin A Sun X Gill G 2009 Sp4-dependent repression of neurotrophin-3 limits dendritic branching Mol Cell Neurosci 42 152 159 19555762 PMC2727929
  45. Safe S Abdelrahim M 2005 Sp transcription factor family and its role in cancer Eur J Cancer 41 2438 2448 16209919
  46. Scarpulla RC 2008 Nuclear control of respiratory chain expression by nuclear respiratory factors and PGC-1-related coactivator Ann NY Acad Sci 1147 321 334 19076454 PMC2853241
  47. Suske G 1999 The Sp-family of transcription factors Gene 238 291 300 10570957
  48. Tsukihara T Aoyama H Yamashita E Tomizaki T Yamaguchi H Shinzawa-Itoh K Nakashima R Yaono R Yoshikawa S 1996 The whole structure of the 13-subunit oxidized cytochrome c oxidase at 2.8 A Science 272 1136 1144 8638158
  49. Virbasius JV Scarpulla RC 1994 Activation of the human mitochondrial transcription factor A gene by nuclear respiratory factors: a potential regulatory link between nuclear and mitochondrial gene expression in organelle biogenesis Proc Natl Acad Sci U S A 91 1309 1313 8108407 PMC43147
  50. Wierstra I 2008 Sp1: emerging roles--beyond constitutive activation of TATA-less housekeeping genes Biochem Biophys Res Commun 372 1 13 18364237
  51. Wikström M Krab K Saraste M 1981 Cytochrome oxidase A Synthesis Academic Press New York
  52. Wong-Riley M 1979 Changes in the visual system of monocularly sutured or enucleated cats demonstrable with cytochrome oxidase histochemistry Brain Research 171 11 28 223730
  53. Wong-Riley MTT 1989 Cytochrome oxidase: an endogenous metabolic marker for neuronal activity Trends Neurosci 12 94 101 2469224
  54. Wong-Riley MTT 2012 Bigenomic regulation of cytochrome c oxidase in neurons and the tight coupling between neuronal activity and energy metabolism Adv Exp Med Biol 748 283 304 22729863 PMC3710587
  55. Wong-Riley M Anderson B Liebl W Huang Z 1998 Neurochemical organization of the macaque striate cortex: Correlation of cytochrome oxidase with Na+K+ATPase, NADPH-diaphorase, nitric oxide synthase, and NMDA receptor subunit 1 Neurosci 83 1025 1045 9502244
  56. Wu Z Puigserver P Andersson U Zhang C Adelmant G Mootha V Troy A Cinti S Lowell B Scarpulla RC Spiegelman BM 1999 Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1 Cell 98 115 124 10412986
  57. Yamada M Amuro N Goto Y Okazaki T 1990 Structural organization of the rat cytochrome c oxidase subunit IV gene J Biol Chem 265 7687 7692 2159010
  58. Yang SJ Liang HL Wong-Riley MTT 2006 Activity-dependent transcriptional regulation of nuclear respiratory factor-1 in cultured rat visual cortical neurons Neurosci 141 1181 1192 16753268

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Authors
Johar, K., Priya, A., Dhar, S., Liu, Q., & Wong‐Riley, M. T. T.
Affiliations
Medical College of Wisconsin (US)
Corresponding author
Wong‐Riley, Margaret T. T.
ORCID
Venue
Journal of Neurochemistry
Publisher
Wiley
Published
2013-09-30
Volume
127
Issue
4
Pages
496-508
ISSN
  • 0022-3042 (ISSN-L)
  • 1471-4159
DOI
10.1111/jnc.12433
PMC
PMC3820366
OpenAlex
W1965025793
Cited by
25
References
1
Citations by year
2025: 1 · 2024: 1 · 2023: 3 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 5 · 2018: 1 · 2017: 1 · 2015: 5 · 2014: 4 · 2013: 1
FWCI
1.26
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Journal of Neurochemistry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of Health (R01 EY018441, T32 EY14537)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Coenzyme Q10 studies and effects
Keywords
Sp4, cytochrome c oxidase, transcriptional regulation, neurons, mitochondrial transcription factors, TFAM, TFB1M, TFB2M, oxidative metabolism, primary neurons
MeSH terms
Animals, Cell Nucleus, Cells, Cultured, Electron Transport Complex IV, DNA-Binding Proteins, Female, High Mobility Group Proteins, Male, Mice, Inbred C57BL, Neurons, Protein Binding, Transcription Factors, Transcription, Genetic, Visual Cortex, Protein Subunits, Cell Line, Tumor, Mice, Sp4 Transcription Factor, Genome, Mitochondrial, Gene Knockdown Techniques

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