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Mitochondrial transcription factors B1 and B2 activate transcription of human mtDNA
Abstract
Characterization of the basic transcription machinery of mammalian mitochondrial DNA (mtDNA) is of fundamental biological interest and may also lead to therapeutic interventions for human diseases associated with mitochondrial dysfunction. Here we report that mitochondrial transcription factors B1 (TFB1M) and B2 (TFB2M) are necessary for basal transcription of mammalian mitochondrial DNA (mtDNA). Human TFB1M and TFB2M are expressed ubiquitously and can each support promoter-specific mtDNA transcription in a pure recombinant in vitro system containing mitochondrial RNA polymerase (POLRMT) and mitochondrial transcription factor A. Both TFB1M and TFB2M interact directly with POLRMT, but TFB2M is at least one order of magnitude more active in promoting transcription than TFB1M. Both factors are highly homologous to bacterial rRNA dimethyltransferases, which suggests that an RNA-modifying enzyme has been recruited during evolution to function as a mitochondrial transcription factor. The presence of two proteins that interact with mammalian POLRMT may allow flexible regulation of mtDNA gene expression in response to the complex physiological demands of mammalian metabolism.
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“Tfam is ubiquitously expressed and absolutely required for mtDNA transcription (8,13).”
From Increased mitochondrial mass in mitochondrial myopathy mice (2002) · cites this paper as [13]
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Self-citationThe impact of mitochondrial genetics on male infertility
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“The basalmachinery responsible for transcription initiation in mammalian mitochondria is a three-component system (3), consisting of the mitochondrial RNA polymerase, mitochondrial transcription factor B2 (TFB2M), and mitochondrial transcription factor A (TFAM) (4).”
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Farge, G., Mehmedović, M., Baclayon, M., van den Wildenberg, S., Roos, W., Gustafsson, C., Wuite, G., & Falkenberg, M. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.05.046 · Cited by 112
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InfluentialSelf-citationJemt, E., Persson, Ö., Shi, Y., Mehmedovic, M., Uhler, J. P., Dávila López, M., Freyer, C., Gustafsson, C. M., Samuelsson, T., & Falkenberg, M. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv804 · Cited by 121
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MethodSelf-citationReplication and Transcription of Human Mitochondrial DNA
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Self-citationExpression and Maintenance of Mitochondrial DNA
Shadel, G. S. (2008) · American Journal Of Pathology · doi:10.2353/ajpath.2008.071163 · Cited by 122
“They also reconstituted specific mitochondrial transcription in vitro using h-mtTFA and a complex of POLRMT with either h-mtTFB1 or h-mtTFB2, with all proteins produced from recombinant sources.(48) Altogether, these seminal studies defined the core human mitochondrial transcription system as a mixed three-component s…”
BackgroundMethodThe post-transcriptional life of mammalian mitochondrial RNA
Rorbach, J., & Minczuk, M. (2012) · Biochemical Journal · doi:10.1042/bj20112208 · Cited by 118
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Self-citationOrganization of DNA in Mammalian Mitochondria
Farge, G., & Falkenberg, M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20112770 · Cited by 118
“Transcription elongation by POLRMT is stimulated by the mitochondrial transcription elongation factor (TEFM), which stabilizes the interactions between elongating POLRMT and template DNA [54,59].”
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“Given the documented roles for the h-mtTFB factors in directing transcription initiation efficiency (2), these changes most likely represent an increase in the rate of mitochondrial transcription that is also driving a increase in transcription-primed mtDNA replication (1).”
BackgroundInfluentialPseudogenes in metazoa: Origin and features
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“mtTFA enhances mtDNA transcription by mitochondrial RNA polymerase in a promoter-specific fashion and in the presence of mitochondrial transcription factor B.(62,63) Since mitochondrial replication and transcription seem to be coupled,(64) mtTFA could be essential for mtDNA replication.”
BackgroundTEFM is a potent stimulator of mitochondrial transcription elongation in vitro
Posse, V., Shahzad, S., Falkenberg, M., Hällberg, B. M., & Gustafsson, C. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv105 · Cited by 107
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MethodSelf-citationMTERF3 Regulates Mitochondrial Ribosome Biogenesis in Invertebrates and Mammals
Wredenberg, A., Lagouge, M., Bratić, A. M., Metodiev, M. D., Spåhr, H., Mourier, A., Freyer, C., Ruzzenente, B., Tain, L. S., Grönke, S., et al. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003178 · Cited by 113
Self-citationStructure, mechanism, and regulation of mitochondrial DNA transcription initiation
Basu, U., Bostwick, A. M., Das, K., Dittenhafer‐Reed, K. E., & Patel, S. S. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.rev120.011202 · Cited by 114
“TFB2M was discovered based on its amino acid sequence homology to MTF1 (47, 48) and after MTF1 was established as the initiation factor in yeast (49, 50).”
GABP Transcription Factor (Nuclear Respiratory Factor 2) Is Required for Mitochondrial Biogenesis
Yang, Z.-F., Drumea, K., Mott, S., Wang, J., & Rosmarin, A. G. (2014) · Molecular and Cellular Biology · doi:10.1128/mcb.00492-12 · Cited by 112
“(Invitrogen) at 5 g/ml at 37°C for 30 to 60 min (19), followed by flow”
BackgroundStructural basis of mitochondrial transcription
Hillen, H. S., Temiakov, D., & Cramer, P. (2018) · Nature Structural & Molecular Biology · doi:10.1038/s41594-018-0122-9 · Cited by 111
The transcription machinery in mammalian mitochondria
Gaspari, M., Larsson, N., & Gustafsson, C. M. (2004) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2004.10.003 · Cited by 111
“The levels of TFAM directly regulate the activity of both TFB1M/POLRMT- and TFB2M/POLRMT-dependent mtDNA transcription both in vivo and in vitro [16].”
InfluentialSelf-citationJoseph, A.-M., Pilegaard, H., Litvintsev, A., Leick, L., & Hood, D. A. (2006) · Essays in Biochemistry · doi:10.1042/bse0420013 · Cited by 112
“It is proposed that Fis1 recruits Drp1 to the mitochondrial outer membrane, where activated Drp1 forms a ring-like complex and conveys signals to (or from) the inner membrane to coordinate mitochondrial membrane fi ssion (modifi ed from [23,25]).”
BackgroundRodríguez-Cuenca, S., Monjo, M., Gianotti, M., Proenza, A. M., & Roca, P. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00175.2006 · Cited by 108
“The nuclear respiratory transcriptional factors NRF1 and GABPA (homologous to the human NRF2) are involved in the expression of many genes related to mitochondrial function and biogenesis, including those encoding subunits of the five respiratory complexes and the mitochondrial transcription factor A (TFAM), a nuclear…”
BackgroundReplication of mitochondrial DNA occurs throughout the mitochondria of cultured human cells
Magnusson, J. (2003) · Experimental Cell Research · doi:10.1016/s0014-4827(03)00249-0 · Cited by 109
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Self-citationO’Brien, L. C., Keeney, P. M., & Bennett, J. P. (2015) · Stem Cells and Development · doi:10.1089/scd.2015.0076 · Cited by 109
“TFB2M showed a slight increase in transcription during differentiation (P = 0.058; Fig.”
BackgroundInfluentialMitochondrial pathways to cardiac recovery: TFAM
Kunkel, G. H., Chaturvedi, P., & Tyagi, S. C. (2016) · Heart Failure Reviews · doi:10.1007/s10741-016-9561-8 · Cited by 105
“These transcription factors directly promote transcription, utilizing POLRMT [10].”
InfluentialViperin, a key player in the antiviral response
Mattijssen, S., & Pruijn, G. J. M. (2011) · Microbes and Infection · doi:10.1016/j.micinf.2011.11.015 · Cited by 105
The human mitochondrial transcriptome and the RNA‐binding proteins that regulate its expression
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Understanding aging: revealing order out of chaos
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Self-citationA compendium of human mitochondrial gene expression machinery with links to disease
Shutt, T. E., & Shadel, G. S. (2010) · Environmental and Molecular Mutagenesis · doi:10.1002/em.20571 · Cited by 100
“It is important to note, however, that h-mtTFB1 and h-mtTFB2 have each retained transcription factor activity in vitro [Falkenberg et al., 2002] and rRNA methyltransferase activity as ascertained in a heterologous Escherichia coli system [Seidel-Rogol et al.”
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Nuclear genes involved in mitochondrial diseases caused by instability of mitochondrial DNA
Rusecka, J. M., Kaliszewska, M., Bartnik, E., & Tońska, K. (2018) · Journal of Applied Genetics · doi:10.1007/s13353-017-0424-3 · Cited by 100
“TFB1M and TFB2M interact directly with POLRMT, help in promoter recognition, and increase transcription efficiency 100–200-fold as compared with RNA polymerase alone (Falkenberg et al. 2002; Litonin et al. 2010).”
NDUFAF7 Methylates Arginine 85 in the NDUFS2 Subunit of Human Complex I
Rhein, V. F., Carroll, J., Ding, S., Fearnley, I. M., & Walker, J. E. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.518803 · Cited by 104
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“Three protein factors, TFAM (2), TFB1M and TFB2M (3), are required for the initiation of mitochondrial transcription at the two promoters (HSP and LSP) placed in the main non-coding region (NCR); the DNA-binding protein mTERF (4) mediates termination of transcription of the ribosomal unit, accounting for the productio…”
BackgroundMechanisms and regulation of human mitochondrial transcription
Tan, B. G., Gustafsson, C., & Falkenberg, M. (2023) · Nature reviews. Molecular cell biology · doi:10.1038/s41580-023-00661-4 · Cited by 87
“A combination of structural, biochemical and in vivo mouse genetics experiments has established that the canonical human mitochondrial promoters LSP and HSP require POLRMT and the two transcription factors TFAM and TFB2M for activity 7,37,39,40,44,46,53–57 .”
InfluentialSelf-citationMitochondria as pharmacological targets in Down syndrome
Valenti, D., Braidy, N., Rasmo, D. D., Signorile, A., Rossi, L., Atanasov, A. G., Volpicella, M., Henrion‐Caude, A., Nabavi, S. M., & Vacca, R. A. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2017.08.014 · Cited by 99
“As TFAM and TFBs are required for basal transcription of mammalian mtDNA [35], their regulation through NRF transcriptional activity is responsible for nucleo-mitochondrial interactions.”
BackgroundThe TFAM-to-mtDNA ratio defines inner-cellular nucleoid populations with distinct activity levels
Brüser, C., Keller‐Findeisen, J., & Jakobs, S. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.110000 · Cited by 98
“Replication-active nucleoids are also transcriptionally active The mitochondrial RNA (mtRNA) polymerase POLRMT and the activation factors TFAM and TFB2M are required for mitochondrial transcription initiation (Falkenberg et al., 2002; Ringel et al., 2011; Shutt and Gray, 2006).”
BackgroundCoordination of mitochondrial biogenesis by PGC-1α in human skeletal muscle: A re-evaluation
Islam, H., Edgett, B. A., & Gurd, B. J. (2018) · Metabolism · doi:10.1016/j.metabol.2017.11.001 · Cited by 99
“pathway also up-regulates the mitochondrial transcription factors B1 (TFB1M) and B2 (TFB2M), essential components of the mtDNA transcriptional machinery [25,26].”
Mandal, S. M., Hegde, M. L., Chatterjee, A., Hegde, P. M., Szczęsny, B., Banerjee, D., Boldogh, I. R., Gao, R., Falkenberg, M., Gustafsson, C. M., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.272179 · Cited by 98
Self-citationGangelhoff, T. A., Mungalachetty, P. S., Nix, J. C., & Churchill, M. E. A. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp157 · Cited by 97
“The later back-to-back discovery and functional analyses of the factors h-mtTFB1 and h-mtTFB2 revealed that both proteins have roles in transcription activation ( 12 ,13).”
BackgroundCore human mitochondrial transcription apparatus is a regulated two-component system in vitro
Shutt, T. E., Lodeiro, M. F., Cotney, J. L., Cameron, C. E., & Shadel, G. S. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0910581107 · Cited by 96
“The h-mtTFA-independent promoter initiation activity of POLRMT and h-mtTFB2 identified implies that the requirements for initiation at the LSP and HSP1 are even more distinct than documented previously (14, 22, 50, 54).”
BackgroundMethodResultInfluentialThe Maintenance of Mitochondrial DNA Integrity and Dynamics by Mitochondrial Membranes
Chapman, J., Ng, Y. S., & Nicholls, T. J. J. (2020) · Life · doi:10.3390/life10090164 · Cited by 100
“Life 2020, 10, 164 21 of 42 Abbreviations 3-MGA 3-methylglutoconic aciduria AD autosomal dominant AR autosomal recessive ATAD3 ATPase family AAA domain-containing protein 3 ATP adenosine triphosphate CK creatine kinase CMT Charcot-Marie-Tooth COX1 cytochrome c oxidase 1 subunit CPEO chronic progressive external ophtha…”
BackgroundHigh levels of TFAM repress mammalian mitochondrial DNA transcription in vivo
Bonekamp, N. A., Jiang, M., Motori, E., García-Villegas, R., Koolmeister, C., Atanassov, I., Mesaros, A., Park, C. B., & Larsson, N. (2021) · Life Science Alliance · doi:10.26508/lsa.202101034 · Cited by 96
“…of mitochondrial function in mammals because of its dual role as a core component of the mitochondrial transcription initiation machinery and as the key factor packaging mtDNA into mitochondrial nucleoids (Falkenberg et al, 2002; Alam et al, 2003; Kukat et al, 2011, 2015; Shi et al, 2012).”
Self-citationGarstka, H. L. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg717 · Cited by 95
“It was demonstrated repeatedly that only about 75% of mtDNA molecules are protected at the TFAM binding site near the LSP and that a consistently lower fraction (30±50%) of the binding site close to HSP is occupied, due to its lower af®nity for the protein (15,47).”
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Mitochondrial Dysfunction: The Road to Alpha-Synuclein Oligomerization in PD
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“TFAM is a phylogenetically conserved protein and is imported to mitochondria which is essential for mtDNA maintenance and directly regulates mtDNA copy number and is absolutely required for transcription initiation at mtDNA promoters [47–49].”
Ramachandran, A., Basu, U., Sultana, S., Nandakumar, D., & Patel, S. S. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw1157 · Cited by 90
“The initiation factor TFB2M is structurally homologous to bacterial RNA methyltransferase ErmC’ (8,10); however, it has lost most of its RNA methyltransferase activity (11) and serves mainly as the transcription initiation factor.”
BackgroundKing, G. A., Shabestari, M. H., Taris, K.-K. H., Pandey, A. K., Venkatesh, S., Thilagavathi, J., Singh, K., Koppisetti, R. K., Temiakov, D., Roos, W. H., et al. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky204 · Cited by 89
Nuclear genes in mitochondrial disorders
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“Based on in vitro studies, transcription of human mtDNA requires a core two-component system (9): a single-subunit RNA polymerase, POLRMT (10), and human mitochondrial transcription factor B2, h-mtTFB2 (or TFB2M) (11, 12).”
BackgroundMethodMatsushima, Y., Garesse, R., & Kaguni, L. S. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m401643200 · Cited by 86
Structure of human mitochondrial RNA polymerase elongation complex
Schwinghammer, K., Cheung, A. C. M., Morozov, Y. I., Agaronyan, K., Temiakov, D., & Cramer, P. (2013) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2683 · Cited by 86
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Coupling the mitochondrial transcription machinery to human disease
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Transcription and transcriptional regulation in plastids
Liere, K., & Börner, T. (2007) · Topics in current genetics · doi:10.1007/4735_2007_0232 · Cited by 82
“Despite poor overall sequence similarity, it recently has been shown that mtTFB factors belong to a family of RNA-methyltransferases (Falkenberg et al. 2002; McCulloch et al. 2002; Rantanen et al. 2003; Seidel-Rogol et al. 2003).”
BackgroundRedox mechanisms of cardiomyocyte mitochondrial protection
Bartz, R. R., Suliman, H. B., & Piantadosi, C. A. (2015) · Frontiers in Physiology · doi:10.3389/fphys.2015.00291 · Cited by 82
“…factor B which enable transcription of the mitochondrial genome (Carter and Avadhani, 1994; Virbasius and Scarpulla, 1994; Dairaghi et al., 1995; Carrodeguas et al., 1996; Shadel and Clayton, 1996; Larsson et al., 1998; Falkenberg et al., 2002; Ekstrand et al., 2004; Gleyzer et al., 2005).”
BackgroundRNase H1 directs origin-specific initiation of DNA replication in human mitochondria
Posse, V., Al-Behadili, A., Uhler, J. P., Clausen, A., Reyes, A., Zeviani, M., Falkenberg, M., & Gustafsson, C. (2019) · PLoS Genetics · doi:10.1371/journal.pgen.1007781 · Cited by 72
Self-citationAccessorizing the human mitochondrial transcription machinery
Bestwick, M. L., & Shadel, G. S. (2013) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2013.03.006 · Cited by 82
“However, multiple lines of evidence now suggest that TFB1M is the primary mitochondrial 12S rRNA methyltransferase important for small subunit ribosome biogenesis and TFB2M is the primary mitochondrial transcription initiation factor [15, 33, 34].”
MTERF2 is a nucleoid component in mammalian mitochondria
Pellegrini, M., Asin-Cayuela, J., Erdjument‐Bromage, H., Tempst, P., Larsson, N., & Gustafsson, C. M. (2009) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2009.01.018 · Cited by 82
“Similarly, addition of the MTERF2 protein failed to affect in vitro transcription from the LSP or HSP promoters using previously described conditions [6].”
BackgroundSelf-citationMitochondrial transcript maturation and its disorders
Haute, L. V., Pearce, S. F., Powell, C. A., D’Souza, A. R., Nicholls, T. J. J., & Minczuk, M. A. (2015) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-015-9859-z · Cited by 79
“Transcription in human mitochondria also requires mitochondrial transcription factor A (TFAM) (Falkenberg et al 2002; Shi et al 2012).”
BackgroundInfluentialArabidopsis Phage-Type RNA Polymerases: Accurate in Vitro Transcription of Organellar Genes
Kühn, K., Bohne, A., Liere, K., Weihe, A., & Börner, T. (2007) · The Plant Cell · doi:10.1105/tpc.106.046839 · Cited by 81
“…in the mitochondria of yeast and mammals, however, depends on the transcriptional cofactor mtTFB (MTF1, TFBM), which is related to rRNA dimethyladenosine transferases (Winkley et al., 1985; Schinkel et al., 1987; Falkenberg et al., 2002; McCulloch et al., 2002; Matsunaga and Jaehning, 2004b).”
BackgroundMethodInfluentialThe implications of mitochondrial DNA copy number regulation during embryogenesis
Carling, P. J., Cree, L. M., & Chinnery, P. F. (2011) · Mitochondrion · doi:10.1016/j.mito.2011.05.004 · Cited by 79
Cotney, J. L., & Shadel, G. S. (2006) · Journal of Molecular Evolution · doi:10.1007/s00239-006-0075-1 · Cited by 80
“Both hmtTFB1 and h-mtTFB2 are homologous to a class of site-specific, rRNA adenine methyltransferases (Falkenberg et al. 2002; McCulloch et al. 2002) and hmtTFB1 has been shown to bind S-adenosylmethionine (SAM) (McCulloch and Shadel 2003) and to possess this enzymatic activity (Seidel-Rogol et al.”
BackgroundResultInfluentialBykhovskaya, Y. (2004) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2004.01.020 · Cited by 80
A novel intermediate in transcription initiation by human mitochondrial RNA polymerase
Morozov, Y. I., Agaronyan, K., Cheung, A. C. M., Anikin, M., Cramer, P., & Temiakov, D. (2014) · Nucleic Acids Research · doi:10.1093/nar/gkt1356 · Cited by 79
PDIP38 Associates with Proteins Constituting the Mitochondrial DNA Nucleoid
Cheng, X., Kanki, T., Fukuoh, A., Ohgaki, K., Takeya, R., Aoki, Y., Hamasaki, N., & Kang, D. (2005) · The Journal of Biochemistry · doi:10.1093/jb/mvi169 · Cited by 77
Barbieri, E., Battistelli, M., Casadei, L., Vallorani, L., Piccoli, G., Guescini, M., Gioacchini, A. M., Polidori, E., Zeppa, S. D., Ceccaroli, P., et al. (2011) · Journal of Aging Research · doi:10.4061/2011/845379 · Cited by 78
“PGC1α induces mitochondrial biogenesis by interacting with several nuclear transcription factors [36–39], and Tfam is involved in the mitochondrial genome transcription [40, 41], replication [42], and it is also crucial for maintaining mitochondrial DNA [43].”
BackgroundTEFM regulates both transcription elongation and RNA processing in mitochondria
Jiang, S., Koolmeister, C., Misic, J., Siira, S. J., Kühl, I., Ramos, E. S., Miranda, M., Jiang, M., Posse, V., Lytovchenko, O., et al. (2019) · EMBO Reports · doi:10.15252/embr.201948101 · Cited by 83
Self-citationWong‐Riley, M. T. T. (2012) · Advances in experimental medicine and biology · doi:10.1007/978-1-4614-3573-0_12 · Cited by 80
“…that encode mitochondrial transcription factors A and B (TFAM, TFB1M, and TFB2M) (Virbasius and Scarpulla 1994; Gleyzer et al 2005), which are nuclear-derived and function inside the mitochondria as regulators of mtDNA transcription and replication (Fisher and Clayton 1988; Falkenberg et al 2002).”
BackgroundMitochondrial DNA metabolism in early development of zebrafish (Danio rerio)
Artuso, L., Romano, A., Verri, T., Domenichini, A., Argenton, F., Santorelli, F. M., & Petruzzella, V. (2012) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2012.03.019 · Cited by 76
“POLRMT cannot interact directly with promoters: it requires the assistance of mitochondrial transcription factor A (TFAM) as well as of one of the two mitochondrial transcription factor B paralogs (TFB2M, also calledmtTFB2) [35–37], which constitute the basalmachinery necessary and sufficient for promoter-specific ini…”
BackgroundMatsushima, Y., Adán, C., Garesse, R., & Kaguni, L. S. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m500569200 · Cited by 76
Lin, P.-C., Lin, J.-K., Yang, S.-H., Wang, H.-S., Li, A. F., & Chang, S. (2008) · International Journal of Colorectal Disease · doi:10.1007/s00384-008-0539-4 · Cited by 76
“Initiation of transcription in mammalian mitochondria depends on three proteins: POLRMT, TFAM, and mitochondrial transcription factor B2 [23, 33 , 34].”
BackgroundKumar, K., Wigfield, S., Gee, H. E., Devlin, C. M., Singleton, D. C., Li, J., Buffa, F. M., Huffman, M., Sinn, A. L., Silver, J. M., et al. (2013) · Journal of Molecular Medicine · doi:10.1007/s00109-013-0996-2 · Cited by 76
Cotney, J. L., McKay, S. E., & Shadel, G. S. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp208 · Cited by 76
Mitochondrial DNA transcription regulation and nucleoid organization
Rebelo, A. P., Dillon, L. M., & Moraes, C. T. (2011) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-011-9330-8 · Cited by 76
“Both TFB1M and TFB2M can stimulate transcription in the presence of TFAM and POLRMT in a reconstituted in vitro transcription system (Falkenberg et al. 2002).”
BackgroundInfluentialMutational screening of the mortalin gene (HSPA9) in Parkinson’s disease
de Mena, L., Coto, E., Sánchez-Ferrero, E., Ribacoba, R., Guisasola, L. M., Salvador, C., Estrada, M. B., & Álvarez, V. (2009) · Journal of Neural Transmission · doi:10.1007/s00702-009-0273-2 · Cited by 75
Papa, S., Rasmo, D. D., Technikova-Dobrova, Z., Panelli, D., Signorile, A., Scacco, S., Petruzzella, V., Papa, F., Palmisano, G., Gnoni, A., et al. (2011) · FEBS Letters · doi:10.1016/j.febslet.2011.09.019 · Cited by 78
“This interacts with the mitochondrial RNA polymerase [97] together with two additional transcription factors (mitochondrial transcription factor TFB1M and TFB2M) and a fraction of PGC-1a found in mitochondria [92].”
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Self-citationTranscription, Processing, and Decay of Mitochondrial RNA in Health and Disease
Barchiesi, A., & Vascotto, C. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20092221 · Cited by 80
“In fact, TFB2M is required for the conformational changes needed for the transcription starting [23].”
BackgroundInfluentialMitochondrial Nucleoid and Transcription Factor A
Kanki, T., Nakayama, H., Sasaki, N., Takio, K., Alam, T. I., Hamasaki, N., & Kang, D. (2004) · Springer eBooks · doi:10.1007/978-3-662-41088-2_7 · Cited by 73
Transcribing β-cell mitochondria in health and disease
Mulder, H. (2017) · Molecular Metabolism · doi:10.1016/j.molmet.2017.05.014 · Cited by 74
“Transcription factor B1 mitochondrial (TFB1M) TFB1M was initially thought to be a transcription factor, hence its name; it facilitates transcription at high concentrations in an in vitro system [70].”
BackgroundAsin-Cayuela, J., Schwend, T., Farge, G., & Gustafsson, C. M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m501145200 · Cited by 73
Self-citationLong-term High-fat-diet Feeding Impairs Mitochondrial Biogenesis in Liver of Male and Female Rats
Nadal-Casellas, A., Amengual-Cladera, E., Proenza, A. M., Lladó, I., & Gianotti, M. (2010) · Cellular Physiology and Biochemistry · doi:10.1159/000320552 · Cited by 72
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Intrinsic Promoter Recognition by a “Core” RNA Polymerase
Matsunaga, M., & Jaehning, J. A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.c400384200 · Cited by 70
Transcription of mammalian messenger RNAs by a nuclear RNA polymerase of mitochondrial origin
Kravchenko, J. E., Rogozin, I. B., Koonin, E. V., & Chumakov, P. M. (2005) · Nature · doi:10.1038/nature03848 · Cited by 71
Mitochondrial DNA mutations in renal disease: an overview
Govers, L. P., Toka, H. R., Hariri, A., Walsh, S. B., & Böckenhauer, D. (2020) · Pediatric Nephrology · doi:10.1007/s00467-019-04404-6 · Cited by 70
“The role of TFAM is to recruit POLRMT to the promoter initiation site in order for TFB2M to melt the promoter [23].”
BackgroundMitochondrial nucleoid and transcription factor A
KANKI, T., NAKAYAMA, H., SASAKI, N., TAKIO, K., ALAM, T. I., HAMASAKI, N., & KANG, D. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1293.007 · Cited by 70
“4); (2) TFAM is able to substitute for Abf2, a TFAM homologue of yeast, which is supposed to mainly play a histone-like role for maintaining mtDNA;3 (3) TFAM is abundant enough to cover mtDNA;19 (4) most mtDNA molecules are associated with TFAM;18 (5) most TFAM is associated with mtDNA;18 and (6) the 50% reduction in…”
BackgroundSex Differences in Brown Adipose Tissue Thermogenic Features During Caloric Restriction
Valle, A., García-Palmer, F., Oliver, J., & Roca, P. (2007) · Cellular Physiology and Biochemistry · doi:10.1159/000099207 · Cited by 70
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Transmission of mitochondrial DNA following assisted reproduction and nuclear transfer
Spikings, E. C., Alderson, J., & John, J. C. S. (2006) · Human Reproduction Update · doi:10.1093/humupd/dml011 · Cited by 72
Non-coding 7S RNA inhibits transcription via mitochondrial RNA polymerase dimerization
Zhu, X., Xie, X., Das, H., Tan, B. G., Shi, Y., Al-Behadili, A., Peter, B., Motori, E., Valenzuela, S., Posse, V., et al. (2022) · Cell · doi:10.1016/j.cell.2022.05.006 · Cited by 69
“In this system, transcription from either LSP or HSP produces a dominant run-off (RO) product corresponding to transcription to the end of the DNA template (Falkenberg et al., 2002).”
Self-citationMitochondrial retrograde signaling regulates neuronal function
Cagin, U., Duncan, O. F., Gatt, A. P., Dionne, M., Sweeney, S. T., & Bateman, J. E. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1505036112 · Cited by 66
Metadata
- Authors
- Falkenberg, M., Gaspari, M., Rantanen, A., Trifunovic, A., Larsson, N.-G., & Gustafsson, C. M.
- Affiliations
- Karolinska Institutet (SE)
- Corresponding author
- Larsson, Nils-Göran
- Gustafsson, Claes M.
- Venue
- Nature Genetics
- Published
- 2002-06-17
- Volume
- 31
- Issue
- 3
- Pages
- 289-294
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2081360068
- Cited by
- 598
- References
- 30
- Citations by year
- 2026: 5 · 2025: 14 · 2024: 14 · 2023: 14 · 2022: 15 · 2021: 18 · 2020: 19 · 2019: 24 · 2018: 23 · 2017: 31 · 2016: 17 · 2015: 26 · 2014: 22 · 2013: 30 · 2012: 30
- FWCI
- 10.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- mitochondrial transcription factors, TFB1M, TFB2M, mitochondrial transcription, mitochondrial RNA polymerase, transcriptional regulation, mitochondrial dysfunction
- MeSH terms
- Amino Acid Sequence, Animals, DNA-Binding Proteins, DNA, Mitochondrial, Humans, Leukocytes, Methyltransferases, Molecular Sequence Data, Promoter Regions, Genetic, Recombinant Proteins, DNA-Directed RNA Polymerases, Transcription Factors, Transcription, Genetic, Sequence Homology, Amino Acid, Mitochondrial Proteins, Mice, In Vitro Techniques
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