Bogenhagen, D. & Clayton, D. A. The number of mitochondrial deoxyribonucleic acid genomes in mouse L and human HeLa cells. Quantitative isolation of mitochondrial deoxyribonucleic acid. J. Biol. Chem. 249, 7991–7995 (1974).

Article  CAS  PubMed  Google Scholar 

Anderson, S. et al. Sequence and organization of the human mitochondrial genome. Nature 290, 457–465 (1981).

Article  CAS  PubMed  Google Scholar 

Reznik, E. et al. Mitochondrial DNA copy number variation across human cancers. eLife 5, e10769 (2016).

Article  PubMed  PubMed Central  Google Scholar 

Silva-Pinheiro, P. et al. A library of base editors for the precise ablation of all protein-coding genes in the mouse mitochondrial genome. Nat. Biomed. Eng. 7, 692–703 (2022).

Article  PubMed  PubMed Central  Google Scholar 

Silva-Pinheiro, P. & Minczuk, M. The potential of mitochondrial genome engineering. Nat Rev. Genet. https://doi.org/10.1038/s41576-021-00432-x (2021).

Ringel, R. et al. Structure of human mitochondrial RNA polymerase. Nature 478, 269–273 (2011).

Article  CAS  PubMed  Google Scholar 

Falkenberg, M. et al. Mitochondrial transcription factors B1 and B2 activate transcription of human mtDNA. Nat. Genet. 31, 289–294 (2002).

Article  CAS  PubMed  Google Scholar 

Gaspari, M., Falkenberg, M., Larsson, N.-G. & Gustafsson, C. M. The mitochondrial RNA polymerase contributes critically to promoter specificity in mammalian cells. EMBO J. 23, 4606–4614 (2004).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gustafsson, C. M., Falkenberg, M. & Larsson, N.-G. Maintenance and expression of mammalian mitochondrial DNA. Annu. Rev. Biochem. 85, 133–160 (2016).

Article  CAS  PubMed  Google Scholar 

Tan, B. G. et al. The human mitochondrial genome contains a second light strand promoter. Mol. Cell 82, 3646–3660.e9 (2022).

Article  CAS  PubMed  Google Scholar 

Liu, Y. et al. The PPR domain of mitochondrial RNA polymerase is an exoribonuclease required for mtDNA replication in Drosophila melanogaster. Nat. Cell Biol. 24, 757–765 (2022).

Article  CAS  PubMed  Google Scholar 

Ojala, D., Montoya, J. & Attardi, G. tRNA punctuation model of RNA processing in human mitochondria. Nature 290, 470–474 (1981).

Article  CAS  PubMed  Google Scholar 

Rackham, O. & Filipovska, A. Organization and expression of the mammalian mitochondrial genome. Nat. Rev. Genet. 23, 606–623 (2022).

Article  CAS  PubMed  Google Scholar 

Holzmann, J. et al. RNase P without RNA: identification and functional reconstitution of the human mitochondrial tRNA processing enzyme. Cell 135, 462–474 (2008).

Article  CAS  PubMed  Google Scholar 

Bhatta, A., Dienemann, C., Cramer, P. & Hillen, H. S. Structural basis of RNA processing by human mitochondrial RNase P. Nat. Struct. Mol. Biol. 28, 713–723 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Brzezniak, L. K., Bijata, M., Szczesny, R. J. & Stepien, P. P. Involvement of human ELAC2 gene product in 3’ end processing of mitochondrial tRNAs. RNA Biol. 8, 616–626 (2011).

Article  CAS  PubMed  Google Scholar 

Ohkubo, A. et al. The FASTK family proteins fine-tune mitochondrial RNA processing. PLoS Genet. 17, e1009873 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Clemente, P. et al. ANGEL2 phosphatase activity is required for non-canonical mitochondrial RNA processing. Nat. Commun. 13, 5750 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Asin-Cayuela, J., Schwend, T., Farge, G. & Gustafsson, C. M. The human mitochondrial transcription termination factor (mTERF) is fully active in vitro in the non-phosphorylated form. J. Biol. Chem. 280, 25499–25505 (2005).

Article  CAS  PubMed  Google Scholar 

Yakubovskaya, E., Mejia, E., Byrnes, J., Hambardjieva, E. & Garcia-Diaz, M. Helix unwinding and base flipping enable human MTERF1 to terminate mitochondrial transcription. Cell 141, 982–993 (2010).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Byrnes, J. & Garcia-Diaz, M. Mitochondrial transcription: how does it end? Transcription 2, 32–36 (2011).

Article  PubMed  Google Scholar 

Guja, K. E. & Garcia-Diaz, M. Hitting the brakes: termination of mitochondrial transcription. Biochim. Biophys. Acta 1819, 939–947 (2012).

Article  CAS  PubMed  Google Scholar 

Terzioglu, M. et al. MTERF1 binds mtDNA to prevent transcriptional interference at the light-strand promoter but is dispensable for rRNA gene transcription regulation. Cell Metab. 17, 618–626 (2013).

Article  CAS  PubMed  Google Scholar 

Mulcair, M. D. et al. A molecular mousetrap determines polarity of termination of DNA replication in E. coli. Cell 125, 1309–1319 (2006).

Article  CAS  PubMed  Google Scholar 

Jemt, E. et al. Regulation of DNA replication at the end of the mitochondrial D-loop involves the helicase TWINKLE and a conserved sequence element. Nucleic Acids Res. 43, 9262–9275 (2015).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Haberle, V. & Stark, A. Eukaryotic core promoters and the functional basis of transcription initiation. Nat. Rev. Mol. Cell Biol. 19, 621–637 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

McShane E. et al. Regulatory principles of human mitochondrial gene expression revealed by kinetic analysis of the RNA life cycle. Preprint at bioRxiv https://doi.org/10.1101/2023.02.09.527880 (2023).

Rubalcava-Gracia, D., García-Villegas, R. & Larsson, N.-G. No role for nuclear transcription regulators in mammalian mitochondria? Mol. Cell 83, 832–842 (2023).

Article  CAS  PubMed  Google Scholar 

Basu, U., Bostwick, A. M., Das, K., Dittenhafer-Reed, K. E. & Patel, S. S. Structure, mechanism, and regulation of mitochondrial DNA transcription initiation. J. Biol. Chem. 295, 18406–18425 (2020).

Article  CAS  PubMed  Google Scholar 

Rath, S. et al. MitoCarta3.0: an updated mitochondrial proteome now with sub-organelle localization and pathway annotations. Nucleic Acids Res. 49, D1541–D1547 (2021).

Article  CAS  PubMed  Google Scholar 

Monroy, G., Spencer, E. & Hurwitz, J. Characteristics of reactions catalyzed by purified guanylyltransferase from vaccinia virus. J. Biol. Chem. 253, 4490–4498 (1978).

Article  CAS  PubMed  Google Scholar 

Montoya, J., Christianson, T., Levens, D., Rabinowitz, M. & Attardi, G. Identification of initiation sites for heavy-strand and light-strand transcription in human mitochondrial DNA. Proc. Natl Acad. Sci. USA 79, 7195–7199 (1982).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Maxam, A. M. & Gilbert, W. A new method for sequencing DNA. Proc. Natl Acad. Sci. USA 74, 560–564 (1977).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chang, D. D. & Clayton, D. A. Precise identification of individual promoters for transcription of each strand of human mitochondrial DNA. Cell 36, 635–643 (1984).

Article  CAS  PubMed  Google Scholar 

Fisher, R. P. & Clayton, D. A. Purification and characterization of human mitochondrial transcription factor 1. Mol. Cell. Biol. 8, 3496–3509 (1988).

CAS  PubMed  PubMed Central  Google Scholar 

Parisi, M. A., Xu, B. & Clayton, D. A. A human mitochondrial transcriptional activator can functionally replace a yeast mitochondrial HMG-box protein both in vivo and in vitro. Mol. Cell. Biol. 13, 1951–1961 (1993).

CAS  PubMed  PubMed Central  Google Scholar 

Sologub, M., Litonin, D., Anikin, M., Mustaev, A. & Temiakov, D. TFB2 is a transient component of the catalytic site of the human mitochondrial RNA polymerase. Cell 139, 934–944 (2009).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Schwinghammer, K. et al. Structure of human mitochondrial RNA polymerase elongation complex. Nat. Struct. Mol. Biol. 20, 1298–1303 (2013).

Article  CAS