Organization and expression of the mammalian mitochondrial genome.
Journal
Nature reviews. Genetics
ISSN: 1471-0064
Titre abrégé: Nat Rev Genet
Pays: England
ID NLM: 100962779
Informations de publication
Date de publication:
10 2022
10 2022
Historique:
accepted:
21
03
2022
pubmed:
24
4
2022
medline:
21
9
2022
entrez:
23
4
2022
Statut:
ppublish
Résumé
The mitochondrial genome encodes core subunits of the respiratory chain that drives oxidative phosphorylation and is, therefore, essential for energy conversion. Advances in high-throughput sequencing technologies and cryoelectron microscopy have shed light on the structure and organization of the mitochondrial genome and revealed unique mechanisms of mitochondrial gene regulation. New animal models of impaired mitochondrial protein synthesis have shown how the coordinated regulation of the cytoplasmic and mitochondrial translation machineries ensures the correct assembly of the respiratory chain complexes. These new technologies and disease models are providing a deeper understanding of mitochondrial genome organization and expression and of the diseases caused by impaired energy conversion, including mitochondrial, neurodegenerative, cardiovascular and metabolic diseases. They also provide avenues for the development of treatments for these conditions.
Identifiants
pubmed: 35459860
doi: 10.1038/s41576-022-00480-x
pii: 10.1038/s41576-022-00480-x
doi:
Substances chimiques
Mitochondrial Proteins
0
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
606-623Informations de copyright
© 2022. Springer Nature Limited.
Références
Vafai, S. B. & Mootha, V. K. Mitochondrial disorders as windows into an ancient organelle. Nature 491, 374–383 (2012).
pubmed: 23151580
doi: 10.1038/nature11707
Ojala, D., Montoya, J. & Attardi, G. tRNA punctuation model of RNA processing in human mitochondria. Nature 290, 470–474 (1981).
pubmed: 7219536
doi: 10.1038/290470a0
Denslow, N., Michaels, G., Montoya, J., Attardi, G. & O’Brien, T. Mechanism of mRNA binding to bovine mitochondrial ribosomes. J. Biol. Chem. 264, 8328–8338 (1989).
pubmed: 2542274
doi: 10.1016/S0021-9258(18)83186-6
Lee, R. G., Rudler, D. L., Rackham, O. & Filipovska, A. Is mitochondrial gene expression coordinated or stochastic? Biochem. Soc. Trans. 46, 1239–1246 (2018).
pubmed: 30301847
doi: 10.1042/BST20180174
Hallberg, B. M. & Larsson, N.-G. Making proteins in the powerhouse. Cell Metab. 20, 226–240 (2014).
pubmed: 25088301
doi: 10.1016/j.cmet.2014.07.001
Rackham, O. et al. Long noncoding RNAs are generated from the mitochondrial genome and regulated by nuclear-encoded proteins. RNA 17, 2085–2093 (2011). The study was the first to report the existence of mitochondrial long non-coding RNAs and their potential roles in gene expression.
pubmed: 22028365
pmcid: 3222122
doi: 10.1261/rna.029405.111
Mercer, T. R. et al. The human mitochondrial transcriptome. Cell 146, 645–658 (2011). This paper comprehensively profiles mitochondrial gene organization and expression in diverse tissues and cell lines with unprecedented detail.
pubmed: 21854988
pmcid: 3160626
doi: 10.1016/j.cell.2011.06.051
Liu, G. et al. Mapping of mitochondrial RNA-protein interactions by digital RNase footprinting. Cell Rep. 5, 839–848 (2013).
pubmed: 24183674
doi: 10.1016/j.celrep.2013.09.036
Rudler, D. L. et al. Fidelity of translation initiation is required for coordinated respiratory complex assembly. Sci. Adv. 5, eaay2118 (2019).
pubmed: 31903419
pmcid: 6924987
doi: 10.1126/sciadv.aay2118
Kuznetsova, I. et al. Simultaneous processing and degradation of mitochondrial RNAs revealed by circularized RNA sequencing. Nucleic Acids Res. 45, 5487–5500 (2017).
pubmed: 28201688
pmcid: 5435911
doi: 10.1093/nar/gkx104
Greber, B. J. et al. The complete structure of the 55S mammalian mitochondrial ribosome. Science 348, 303–308 (2015).
pubmed: 25837512
doi: 10.1126/science.aaa3872
Amunts, A., Brown, A., Toots, J., Scheres, S. H. W. & Ramakrishnan, V. Ribosome. The structure of the human mitochondrial ribosome. Science 348, 95–98 (2015). The 2015 papers by Greber et al. and Amunts et al. were the first to report the cryoEM structure of the mammalian mitochondrial ribosome, identifying new and unexpected features of organelle translation.
pubmed: 25838379
pmcid: 4501431
doi: 10.1126/science.aaa1193
Kummer, E. et al. Unique features of mammalian mitochondrial translation initiation revealed by cryo-EM. Nature 560, 263–267 (2018).
pubmed: 30089917
doi: 10.1038/s41586-018-0373-y
Perks, K. L. et al. PTCD1 is required for 16S rRNA maturation complex stability and mitochondrial ribosome assembly. Cell Rep. 23, 127–142 (2018).
pubmed: 29617655
doi: 10.1016/j.celrep.2018.03.033
Kühl, I. et al. Transcriptomic and proteomic landscape of mitochondrial dysfunction reveals secondary coenzyme Q deficiency in mammals. eLife 6, 1494 (2017).
doi: 10.7554/eLife.30952
Mok, B. Y. et al. A bacterial cytidine deaminase toxin enables CRISPR-free mitochondrial base editing. Nature 583, 631–637 (2020). This Article describes a new approach to modulating the mitochondrial genome, opening the way to treating diseases caused by mutations in mtDNA.
pubmed: 32641830
pmcid: 7381381
doi: 10.1038/s41586-020-2477-4
Bacman, S. R. et al. MitoTALEN reduces mutant mtDNA load and restores tRNA
pubmed: 30250143
pmcid: 6942693
doi: 10.1038/s41591-018-0166-8
Nissanka, N., Minczuk, M. & Moraes, C. T. Mechanisms of mitochondrial DNA deletion formation. Trends Genet. 35, 235–244 (2019).
pubmed: 30691869
doi: 10.1016/j.tig.2019.01.001
Silva-Pinheiro, P. & Minczuk, M. The potential of mitochondrial genome engineering. Nat. Rev. Genet. 23, 199–214 (2022). This Article provides a comprehensive review of the potential new tools for mitochondrial genome editing and their applications in biology and in disease treatments.
pubmed: 34857922
doi: 10.1038/s41576-021-00432-x
Gustafsson, C. M., Falkenberg, M. & Larsson, N.-G. Maintenance and expression of mammalian mitochondrial DNA. Annu. Rev. Biochem. 85, 1–28 (2016).
doi: 10.1146/annurev-biochem-060815-014402
Crews, S., Ojala, D., Posakony, J., Nishiguchi, J. & Attardi, G. Nucleotide sequence of a region of human mitochondrial DNA containing the precisely identified origin of replication. Nature 277, 192–198 (1979).
pubmed: 551247
doi: 10.1038/277192a0
Anderson, S. et al. Sequence and organization of the human mitochondrial genome. Nature 290, 457–465 (1981).
pubmed: 7219534
doi: 10.1038/290457a0
Montoya, J., Ojala, D. & Attardi, G. Distinctive features of the 5′-terminal sequences of the human mitochondrial mRNAs. Nature 290, 465–470 (1981).
pubmed: 7219535
doi: 10.1038/290465a0
Temperley, R. J., Wydro, M., Lightowlers, R. N. & Chrzanowska-Lightowlers, Z. M. Human mitochondrial mRNAs — like members of all families, similar but different. Biochim. Biophys. Acta 1797, 1081–1085 (2010).
pubmed: 20211597
pmcid: 3003153
doi: 10.1016/j.bbabio.2010.02.036
Kukat, C. et al. Cross-strand binding of TFAM to a single mtDNA molecule forms the mitochondrial nucleoid. Proc. Natl Acad. Sci. USA 112, 11288–11293 (2015).
pubmed: 26305956
pmcid: 4568684
doi: 10.1073/pnas.1512131112
Kaufman, B. A. et al. The mitochondrial transcription factor TFAM coordinates the assembly of multiple DNA molecules into nucleoid-like structures. Mol. Biol. Cell 18, 3225–3236 (2007).
pubmed: 17581862
pmcid: 1951767
doi: 10.1091/mbc.e07-05-0404
Parisi, M. & Clayton, D. Similarity of human mitochondrial transcription factor 1 to high mobility group proteins. Science 252, 965–969 (1991).
pubmed: 2035027
doi: 10.1126/science.2035027
Bogenhagen, D. F. Mitochondrial DNA nucleoid structure. Biochim. Biophys. Acta 1819, 914–920 (2012).
pubmed: 22142616
doi: 10.1016/j.bbagrm.2011.11.005
Jiang, M. et al. The mitochondrial single-stranded DNA binding protein is essential for initiation of mtDNA replication. Sci. Adv. 7, eabf8631 (2021).
pubmed: 34215584
doi: 10.1126/sciadv.abf8631
Yasukawa, T. & Kang, D. An overview of mammalian mitochondrial DNA replication mechanisms. J. Biochem. 164, 183–193 (2018).
pubmed: 29931097
pmcid: 6094444
doi: 10.1093/jb/mvy058
Viscomi, C. & Zeviani, M. MtDNA-maintenance defects: syndromes and genes. J. Inherit. Metab. Dis. 40, 587–599 (2017).
pubmed: 28324239
pmcid: 5500664
doi: 10.1007/s10545-017-0027-5
Hillen, H. S., Morozov, Y. I., Sarfallah, A., Temiakov, D. & Cramer, P. Structural basis of mitochondrial transcription initiation. Cell 171, 1072–1081.e10 (2017). This paper describes a detailed molecular mechanism of mitochondrial transcription initiation.
pubmed: 29149603
pmcid: 6590061
doi: 10.1016/j.cell.2017.10.036
Kuehl, I. et al. POLRMT regulates the switch between replication primer formation and gene expression of mammalian mtDNA. Sci. Adv. 2, e1600963 (2016).
doi: 10.1126/sciadv.1600963
Minczuk, M. et al. TEFM (c17orf42) is necessary for transcription of human mtDNA. Nucleic Acids Res. 39, 4284–4299 (2011).
pubmed: 21278163
pmcid: 3105396
doi: 10.1093/nar/gkq1224
Jiang, S. et al. TEFM regulates both transcription elongation and RNA processing in mitochondria. EMBO Rep. 20, e48101 (2019).
pubmed: 31036713
pmcid: 6549021
doi: 10.15252/embr.201948101
Agaronyan, K., Morozov, Y. I., Anikin, M. & Temiakov, D. Mitochondrial biology. Replication–transcription switch in human mitochondria. Science 347, 548–551 (2015).
pubmed: 25635099
pmcid: 4677687
doi: 10.1126/science.aaa0986
Posse, V., Shahzad, S., Falkenberg, M., Hällberg, B. M. & Gustafsson, C. M. TEFM is a potent stimulator of mitochondrial transcription elongation in vitro. Nucleic Acids Res. 43, 2615–2624 (2015).
pubmed: 25690892
pmcid: 4357710
doi: 10.1093/nar/gkv105
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).
pubmed: 20550934
pmcid: 2887341
doi: 10.1016/j.cell.2010.05.018
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).
pubmed: 23562081
doi: 10.1016/j.cmet.2013.03.006
Shi, Y. et al. Mitochondrial transcription termination factor 1 directs polar replication fork pausing. Nucleic Acids Res. 44, 5732–5742 (2016).
pubmed: 27112570
pmcid: 4937320
doi: 10.1093/nar/gkw302
Rackham, O. et al. Hierarchical RNA processing is required for mitochondrial ribosome assembly. Cell Rep. 16, 1874–1890 (2016). This paper is the first report of in vivo hierarchical RNA processing in mitochondria that links transcription to mitochondrial ribosome assembly.
pubmed: 27498866
doi: 10.1016/j.celrep.2016.07.031
Gammage, P. A., Moraes, C. T. & Minczuk, M. Mitochondrial genome engineering: the revolution may not be CRISPR-ized. Trends Genet. 34, 101–110 (2018).
pubmed: 29179920
pmcid: 5783712
doi: 10.1016/j.tig.2017.11.001
Holzmann, J. et al. RNase P without RNA: identification and functional reconstitution of the human mitochondrial tRNA processing enzyme. Cell 135, 462–474 (2008). This Article describes the first report of the unique proteinaceous RNase P complex found in human mitochondria, which is devoid of a catalytic RNA.
pubmed: 18984158
doi: 10.1016/j.cell.2008.09.013
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). This paper reports the complete atomic structure of the mitochondrial RNase P complex revealed by cryoEM.
pubmed: 34489609
pmcid: 8437803
doi: 10.1038/s41594-021-00637-y
Reinhard, L., Sridhara, S. & Hallberg, B. M. Structure of the nuclease subunit of human mitochondrial RNase P. Nucleic Acids Res. 43, 5664–5672 (2015).
pubmed: 25953853
pmcid: 4477676
doi: 10.1093/nar/gkv481
Li, F., Liu, X., Zhou, W., Yang, X. & Shen, Y. Auto-inhibitory mechanism of the human mitochondrial RNase P protein complex. Sci. Rep. 5, 9878 (2015).
pubmed: 25928769
pmcid: 4415599
doi: 10.1038/srep09878
Rossmanith, W. Localization of human RNase Z isoforms: dual nuclear/mitochondrial targeting of the ELAC2 gene product by alternative translation initiation. PLoS ONE 6, e19152 (2011).
pubmed: 21559454
pmcid: 3084753
doi: 10.1371/journal.pone.0019152
Siira, S. J. et al. Concerted regulation of mitochondrial and nuclear non-coding RNAs by a dual-targeted RNase Z. EMBO Rep. 19, e46198 (2018).
pubmed: 30126926
pmcid: 6172459
doi: 10.15252/embr.201846198
Sanchez, M. I. G. L. et al. RNA processing in human mitochondria. Cell Cycle 10, 2904–2916 (2011).
pubmed: 21857155
doi: 10.4161/cc.10.17.17060
Jourdain, A. A. et al. The FASTK family of proteins: emerging regulators of mitochondrial RNA biology. Nucleic Acids Res. 45, gkx772 (2017).
doi: 10.1093/nar/gkx772
Ohkubo, A. et al. The FASTK family proteins fine-tune mitochondrial RNA processing. PLoS Genet. 17, e1009873 (2021).
pubmed: 34748562
pmcid: 8601606
doi: 10.1371/journal.pgen.1009873
Antonicka, H. & Shoubridge, E. A. Mitochondrial RNA granules are centers for posttranscriptional RNA processing and ribosome biogenesis. Cell Rep. 10, 920–932 (2015). This paper provides a detailed study of new RNA-binding proteins that are components of the mitochondrial granules that regulate gene expression and ribosome biogenesis.
pubmed: 25683715
doi: 10.1016/j.celrep.2015.01.030
Rey, T. et al. Mitochondrial RNA granules are fluid condensates positioned by membrane dynamics. Nat. Cell Biol. 22, 1180–1186 (2020).
pubmed: 32989247
pmcid: 7610405
doi: 10.1038/s41556-020-00584-8
Bogenhagen, D. F., Martin, D. W. & Koller, A. Initial steps in RNA processing and ribosome assembly occur at mitochondrial DNA nucleoids. Cell Metab. 19, 618–629 (2014).
pubmed: 24703694
doi: 10.1016/j.cmet.2014.03.013
Nagaike, T. et al. Identification and characterization of mammalian mitochondrial tRNA nucleotidyltransferases. J. Biol. Chem. 276, 40041–40049 (2001).
pubmed: 11504732
doi: 10.1074/jbc.M106202200
Suzuki, T. et al. Complete chemical structures of human mitochondrial tRNAs. Nat. Commun. 11, 4269 (2020). The Article provides the most comprehensive account to date of mitochondrial tRNA modifications, validated by mass spectrometry.
pubmed: 32859890
pmcid: 7455718
doi: 10.1038/s41467-020-18068-6
Suzuki, T., Nagao, A. & Suzuki, T. Human mitochondrial tRNAs: biogenesis, function, structural aspects, and diseases. Annu. Rev. Genet. 45, 299–329 (2011).
pubmed: 21910628
doi: 10.1146/annurev-genet-110410-132531
Schöller, E. et al. Balancing of mitochondrial translation through METTL8-mediated m3C modification of mitochondrial tRNAs. Mol. Cell 81, 4810–4825.e12 (2021).
pubmed: 34774131
doi: 10.1016/j.molcel.2021.10.018
Bohnsack, M. T. & Sloan, K. E. The mitochondrial epitranscriptome: the roles of RNA modifications in mitochondrial translation and human disease. Cell Mol. Life Sci. 75, 241–260 (2018).
pubmed: 28752201
doi: 10.1007/s00018-017-2598-6
Vilardo, E. et al. A subcomplex of human mitochondrial RNase P is a bifunctional methyltransferase–extensive moonlighting in mitochondrial tRNA biogenesis. Nucleic Acids Res. 40, 11583–11593 (2012).
pubmed: 23042678
pmcid: 3526285
doi: 10.1093/nar/gks910
Nakano, S. et al. NSUN3 methylase initiates 5-formylcytidine biogenesis in human mitochondrial tRNAMet. Nat. Chem. Biol. 12, 546–551 (2016).
pubmed: 27214402
doi: 10.1038/nchembio.2099
Kawarada, L. et al. ALKBH1 is an RNA dioxygenase responsible for cytoplasmic and mitochondrial tRNA modifications. Nucleic Acids Res. 45, 7401–7415 (2017).
pubmed: 28472312
pmcid: 5499545
doi: 10.1093/nar/gkx354
Haag, S. et al. NSUN3 and ABH1 modify the wobble position of mt-tRNA
pubmed: 27497299
pmcid: 5048346
doi: 10.15252/embj.201694885
Yarham, J. W. et al. Defective i6A37 modification of mitochondrial and cytosolic tRNAs results from pathogenic mutations in TRIT1 and its substrate tRNA. PLoS Genet. 10, e1004424 (2014).
pubmed: 24901367
pmcid: 4046958
doi: 10.1371/journal.pgen.1004424
LenarČiČ, T. et al. Stepwise maturation of the peptidyl transferase region of human mitoribosomes. Nat. Commun. 12, 3671 (2021).
pubmed: 34135320
pmcid: 8208988
doi: 10.1038/s41467-021-23811-8
Zaganelli, S. et al. The pseudouridine synthase RPUSD4 is an essential component of mitochondrial RNA granules. J. Biol. Chem. 292, 4519–4532 (2017).
pubmed: 28082677
pmcid: 5377769
doi: 10.1074/jbc.M116.771105
Antonicka, H. et al. A pseudouridine synthase module is essential for mitochondrial protein synthesis and cell viability. EMBO Rep. 18, 28–38 (2017).
pubmed: 27974379
doi: 10.15252/embr.201643391
Bar-Yaacov, D. et al. Mitochondrial 16S rRNA is methylated by tRNA methyltransferase TRMT61B in all vertebrates. PLoS Biol. 14, e1002557 (2016).
pubmed: 27631568
pmcid: 5025228
doi: 10.1371/journal.pbio.1002557
Lee, K.-W. & Bogenhagen, D. F. Assignment of 2′-O-methyltransferases to modification sites on the mammalian mitochondrial large subunit 16S ribosomal RNA (rRNA). J. Biol. Chem. 289, 24936–24942 (2014).
pubmed: 25074936
pmcid: 4155661
doi: 10.1074/jbc.C114.581868
Metodiev, M. D. et al. NSUN4 is a dual function mitochondrial protein required for both methylation of 12S rRNA and coordination of mitoribosomal assembly. PLoS Genet. 10, e1004110 (2014).
pubmed: 24516400
pmcid: 3916286
doi: 10.1371/journal.pgen.1004110
Laptev, I. et al. METTL15 interacts with the assembly intermediate of murine mitochondrial small ribosomal subunit to form m4C840 12S rRNA residue. Nucleic Acids Res. 48, 8022–8034 (2020).
pubmed: 32573735
pmcid: 7641309
doi: 10.1093/nar/gkaa522
Metodiev, M. et al. Methylation of 12S rRNA is necessary for in vivo stability of the small subunit of the mammalian mitochondrial ribosome. Cell Metab. 9, 386–397 (2009).
pubmed: 19356719
doi: 10.1016/j.cmet.2009.03.001
Powell, C. A. & Minczuk, M. TRMT2B is responsible for both tRNA and rRNA m
pubmed: 31948311
pmcid: 7237155
doi: 10.1080/15476286.2020.1712544
Temperley, R., Richter, R., Dennerlein, S., Lightowlers, R. N. & Chrzanowska-Lightowlers, Z. M. Hungry codons promote frameshifting in human mitochondrial ribosomes. Science 327, 301–301 (2010).
pubmed: 20075246
doi: 10.1126/science.1180674
Chang, J. H. & Tong, L. Mitochondrial poly(A) polymerase and polyadenylation. Biochim. Biophys. Acta 1819, 992–997 (2012).
pubmed: 22172994
doi: 10.1016/j.bbagrm.2011.10.012
Ruzzenente, B. et al. LRPPRC is necessary for polyadenylation and coordination of translation of mitochondrial mRNAs. EMBO J. 31, 443–456 (2012).
pubmed: 22045337
doi: 10.1038/emboj.2011.392
Sasarman, F. et al. LRPPRC and SLIRP interact in a ribonucleoprotein complex that regulates posttranscriptional gene expression in mitochondria. Mol. Biol. Cell 21, 1315–1323 (2010).
pubmed: 20200222
pmcid: 2854090
doi: 10.1091/mbc.e10-01-0047
Siira, S. J. et al. LRPPRC-mediated folding of the mitochondrial transcriptome. Nat. Commun. 8, 1532 (2017).
pubmed: 29146908
pmcid: 5691074
doi: 10.1038/s41467-017-01221-z
Lagouge, M. et al. SLIRP regulates the rate of mitochondrial protein synthesis and protects LRPPRC from degradation. PLoS Genet. 11, e1005423 (2015).
pubmed: 26247782
pmcid: 4527767
doi: 10.1371/journal.pgen.1005423
Aibara, S., Singh, V., Modelska, A. & Amunts, A. Structural basis of mitochondrial translation. eLife 9, e58362 (2020).
pubmed: 32812867
pmcid: 7438116
doi: 10.7554/eLife.58362
Jourdain, A. A. et al. A mitochondria-specific isoform of FASTK is present in mitochondrial RNA granules and regulates gene expression and function. Cell Rep. 10, 1110–1121 (2015).
pubmed: 25704814
doi: 10.1016/j.celrep.2015.01.063
O’Reilly, F. J. et al. In-cell architecture of an actively transcribing–translating expressome. Science 369, 554–557 (2020).
pubmed: 32732422
pmcid: 7115962
doi: 10.1126/science.abb3758
Lee, R. G. et al. Cardiolipin is required for membrane docking of mitochondrial ribosomes and protein synthesis. J. Cell Sci. 133, jcs240374 (2020).
pubmed: 32576663
doi: 10.1242/jcs.240374
Suzuki, T. et al. Analysis of the mammalian mitochondrial ribosome: identification of protein components in the 28S small subunit. J. Biol. Chem. 276, 33181–33195 (2001).
pubmed: 11402041
doi: 10.1074/jbc.M103236200
Brown, A. et al. Structure of the large ribosomal subunit from human mitochondria. Science 346, 718–722 (2014).
pubmed: 25278503
pmcid: 4246062
doi: 10.1126/science.1258026
Greber, B. J. et al. The complete structure of the large subunit of the mammalian mitochondrial ribosome. Nature 515, 283–286 (2014).
pubmed: 25271403
doi: 10.1038/nature13895
Rorbach, J. et al. Human mitochondrial ribosomes can switch their structural RNA composition. Proc. Natl Acad. Sci. USA 113, 12198–12201 (2016).
pubmed: 27729525
pmcid: 5087001
doi: 10.1073/pnas.1609338113
Bogenhagen, D. F., Ostermeyer-Fay, A. G., Haley, J. D. & Garcia-Diaz, M. Kinetics and mechanism of mammalian mitochondrial ribosome assembly. Cell Rep. 22, 1935–1944 (2018). This paper describes detailed SILAC pulse-labelling experiments revealing the import and assembly rates of mitochondrial proteins into mitoribosomes.
pubmed: 29444443
pmcid: 5855118
doi: 10.1016/j.celrep.2018.01.066
Brown, A. et al. Structures of the human mitochondrial ribosome in native states of assembly. Nat. Struct. Mol. Biol. 24, 866–869 (2017).
pubmed: 28892042
pmcid: 5633077
doi: 10.1038/nsmb.3464
Hillen, H. S. et al. Structural basis of GTPase-mediated mitochondrial ribosome biogenesis and recycling. Nat. Commun. 12, 3672 (2021).
pubmed: 34135319
pmcid: 8209004
doi: 10.1038/s41467-021-23702-y
Cipullo, M., Gesé, G. V., Khawaja, A., Hällberg, B. M. & Rorbach, J. Structural basis for late maturation steps of the human mitoribosomal large subunit. Nat. Commun. 12, 3673 (2021).
pubmed: 34135318
pmcid: 8209036
doi: 10.1038/s41467-021-23617-8
Chandrasekaran, V. et al. Visualizing formation of the active site in the mitochondrial ribosome. eLife 10, e68806 (2021).
pubmed: 34609277
pmcid: 8492066
doi: 10.7554/eLife.68806
Cheng, J., Berninghausen, O. & Beckmann, R. A distinct assembly pathway of the human 39S late pre-mitoribosome. Nat. Commun. 12, 4544 (2021).
pubmed: 34315873
pmcid: 8316566
doi: 10.1038/s41467-021-24818-x
Kummer, E. & Ban, N. Mechanisms and regulation of protein synthesis in mitochondria. Nat. Rev. Mol. Cell Biol. 22, 307–325 (2021).
pubmed: 33594280
doi: 10.1038/s41580-021-00332-2
Khawaja, A. et al. Distinct pre-initiation steps in human mitochondrial translation. Nat. Commun. 11, 2932 (2020).
pubmed: 32522994
pmcid: 7287080
doi: 10.1038/s41467-020-16503-2
Christian, B. E. & Spremulli, L. L. Evidence for an active role of IF3mt in the initiation of translation in mammalian mitochondria. Biochemistry 48, 3269–3278 (2009).
pubmed: 19239245
doi: 10.1021/bi8023493
Tucker, E. J. et al. Mutations in MTFMT underlie a human disorder of formylation causing impaired mitochondrial translation. Cell Metab. 14, 428–434 (2011).
pubmed: 21907147
pmcid: 3486727
doi: 10.1016/j.cmet.2011.07.010
Sasarman, F., Antonicka, H. & Shoubridge, E. A. The A3243G tRNA
pubmed: 18753147
doi: 10.1093/hmg/ddn265
Kummer, E., Schubert, K. N., Schoenhut, T., Scaiola, A. & Ban, N. Structural basis of translation termination, rescue, and recycling in mammalian mitochondria. Mol. Cell 81, 2566–2582.e6 (2021).
pubmed: 33878294
doi: 10.1016/j.molcel.2021.03.042
Itoh, Y. et al. Mechanism of membrane-tethered mitochondrial protein synthesis. Science 371, 846–849 (2021).
pubmed: 33602856
pmcid: 7610362
doi: 10.1126/science.abe0763
Soleimanpour-Lichaei, H. R. et al. mtRF1a is a human mitochondrial translation release factor decoding the major termination codons UAA and UAG. Mol. Cell 27, 745–757 (2007). This paper describes the characterization of a mitochondrial translation release factor that acts at the mitochondrial UAA/UAG codons for translation termination.
pubmed: 17803939
pmcid: 1976341
doi: 10.1016/j.molcel.2007.06.031
Akabane, S., Ueda, T., Nierhaus, K. H. & Takeuchi, N. Ribosome rescue and translation termination at non-standard stop codons by ICT1 in mammalian mitochondria. PLoS Genet. 10, e1004616 (2014).
pubmed: 25233460
pmcid: 4169044
doi: 10.1371/journal.pgen.1004616
Young, D. J. et al. Bioinformatic, structural, and functional analyses support release factor-like MTRF1 as a protein able to decode nonstandard stop codons beginning with adenine in vertebrate mitochondria. RNA 16, 1146–1155 (2010).
pubmed: 20421313
pmcid: 2874167
doi: 10.1261/rna.1970310
Desai, N. et al. Elongational stalling activates mitoribosome-associated quality control. Science 370, 1105–1110 (2020).
pubmed: 33243891
pmcid: 7116630
doi: 10.1126/science.abc7782
Matic, S. et al. Mice lacking the mitochondrial exonuclease MGME1 accumulate mtDNA deletions without developing progeria. Nat. Commun. 9, 1202 (2018).
pubmed: 29572490
pmcid: 5865154
doi: 10.1038/s41467-018-03552-x
Nicholls, T. J. et al. Linear mtDNA fragments and unusual mtDNA rearrangements associated with pathological deficiency of MGME1 exonuclease. Hum. Mol. Genet. 23, 6147–6162 (2014).
pubmed: 24986917
pmcid: 4222359
doi: 10.1093/hmg/ddu336
Szczesny, R. J. et al. Identification of a novel human mitochondrial endo-/exonuclease Ddk1/c20orf72 necessary for maintenance of proper 7S DNA levels. Nucleic Acids Res. 41, 3144–3161 (2013).
pubmed: 23358826
pmcid: 3597694
doi: 10.1093/nar/gkt029
Szczesny, R. J. et al. Human mitochondrial RNA turnover caught in flagranti: involvement of hSuv3p helicase in RNA surveillance. Nucleic Acids Res. 38, 279–298 (2010).
pubmed: 19864255
doi: 10.1093/nar/gkp903
Borowski, L. S. L., Dziembowski, A. A., Hejnowicz, M. S. M., Stepien, P. P. P. & Szczesny, R. J. R. Human mitochondrial RNA decay mediated by PNPase–hSuv3 complex takes place in distinct foci. Nucleic Acids Res. 41, 1223–1240 (2012).
pubmed: 23221631
pmcid: 3553951
doi: 10.1093/nar/gks1130
Nicholls, T. J. et al. Dinucleotide degradation by REXO2 maintains promoter specificity in mammalian mitochondria. Mol. Cell 76, 784–796.e6 (2019).
pubmed: 31588022
pmcid: 6900737
doi: 10.1016/j.molcel.2019.09.010
Chujo, T. et al. LRPPRC/SLIRP suppresses PNPase-mediated mRNA decay and promotes polyadenylation in human mitochondria. Nucleic Acids Res. 40, 8033–8047 (2012).
pubmed: 22661577
pmcid: 3439899
doi: 10.1093/nar/gks506
Pietras, Z. et al. Dedicated surveillance mechanism controls G-quadruplex forming non-coding RNAs in human mitochondria. Nat. Commun. 9, 2558 (2018).
pubmed: 29967381
pmcid: 6028389
doi: 10.1038/s41467-018-05007-9
Rorbach, J., Nicholls, T. J. J. & Minczuk, M. PDE12 removes mitochondrial RNA poly(A) tails and controls translation in human mitochondria. Nucleic Acids Res. 39, 7750–7763 (2011).
pubmed: 21666256
pmcid: 3177208
doi: 10.1093/nar/gkr470
Fiedler, M., Rossmanith, W., Wahle, E. & Rammelt, C. Mitochondrial poly(A) polymerase is involved in tRNA repair. Nucleic Acids Res. 43, 9937–9949 (2015).
pubmed: 26354863
pmcid: 4787750
Pearce, S. F. et al. Maturation of selected human mitochondrial tRNAs requires deadenylation. eLife 6, e27596 (2017).
pubmed: 28745585
pmcid: 5544427
doi: 10.7554/eLife.27596
Levy, S. et al. Identification of LACTB2, a metallo-β-lactamase protein, as a human mitochondrial endoribonuclease. Nucleic Acids Res. 44, 1813–1832 (2016).
pubmed: 26826708
pmcid: 4770246
doi: 10.1093/nar/gkw050
Gorman, G. S. et al. Mitochondrial diseases. Nat. Rev. Dis. Prim. 2, 16080 (2016).
pubmed: 27775730
doi: 10.1038/nrdp.2016.80
Knott, G. J. & Doudna, J. A. CRISPR-Cas guides the future of genetic engineering. Science 361, 866–869 (2018).
pubmed: 30166482
pmcid: 6455913
doi: 10.1126/science.aat5011
Hagström, E., Freyer, C., Battersby, B. J., Stewart, J. B. & Larsson, N.-G. No recombination of mtDNA after heteroplasmy for 50 generations in the mouse maternal germline. Nucleic Acids Res. 42, 1111–1116 (2014).
pubmed: 24163253
doi: 10.1093/nar/gkt969
Wallis, C. P., Scott, L. H., Filipovska, A. & Rackham, O. Manipulating and elucidating mitochondrial gene expression with engineered proteins. Phil. Trans. R. Soc. B 375, 20190185 (2020).
pubmed: 31787043
doi: 10.1098/rstb.2019.0185
Rahman, J. & Rahman, S. Mitochondrial medicine in the omics era. Lancet 391, 2560–2574 (2018).
pubmed: 29903433
doi: 10.1016/S0140-6736(18)30727-X
Metodiev, M. D. et al. Recessive mutations in TRMT10C cause defects in mitochondrial RNA processing and multiple respiratory chain deficiencies. Am. J. Hum. Genet. 98, 993–1000 (2016).
pubmed: 27132592
pmcid: 4863561
doi: 10.1016/j.ajhg.2016.03.010
Haack, T. B. et al. ELAC2 mutations cause a mitochondrial RNA processing defect associated with hypertrophic cardiomyopathy. Am. J. Hum. Genet. 93, 211–223 (2013).
pubmed: 23849775
pmcid: 3738821
doi: 10.1016/j.ajhg.2013.06.006
Dotto, V. D. et al. SSBP1 mutations cause mtDNA depletion underlying a complex optic atrophy disorder. J. Clin. Investig. 130, 108–125 (2020).
pubmed: 31550240
doi: 10.1172/JCI128514
Lake, N. J. et al. Biallelic mutations in MRPS34 lead to instability of the small mitoribosomal subunit and Leigh syndrome. Am. J. Hum. Genet. 101, 239–254 (2017).
pubmed: 28777931
pmcid: 5544391
doi: 10.1016/j.ajhg.2017.07.005
Suomalainen, A. & Battersby, B. J. Mitochondrial diseases: the contribution of organelle stress responses to pathology. Nat. Rev. Mol. Cell Biol. 19, 77–92 (2018).
pubmed: 28792006
doi: 10.1038/nrm.2017.66
Gustafson, M. A., Sullivan, E. D. & Copeland, W. C. Consequences of compromised mitochondrial genome integrity. DNA Repair 93, 102916 (2020).
pubmed: 33087282
pmcid: 7587307
doi: 10.1016/j.dnarep.2020.102916
Oláhová, M. et al. POLRMT mutations impair mitochondrial transcription causing neurological disease. Nat. Commun. 12, 1135 (2021).
pubmed: 33602924
pmcid: 7893070
doi: 10.1038/s41467-021-21279-0
Park, C. B. et al. Identification of a rare homozygous c.790 C>T variation in the TFB2M gene in Korean patients with autism spectrum disorder. Biochem. Biophys. Res. Commun. 507, 148–154 (2018).
pubmed: 30414672
doi: 10.1016/j.bbrc.2018.10.194
Nicholas, L. M. et al. Mitochondrial transcription factor B2 is essential for mitochondrial and cellular function in pancreatic β-cells. Mol. Metab. 6, 651–663 (2017).
pubmed: 28702322
pmcid: 5485242
doi: 10.1016/j.molmet.2017.05.005
Deutschmann, A. J. et al. Mutation or knock-down of 17β-hydroxysteroid dehydrogenase type 10 cause loss of MRPP1 and impaired processing of mitochondrial heavy strand transcripts. Hum. Mol. Genet. 23, 3618–3628 (2014).
pubmed: 24549042
doi: 10.1093/hmg/ddu072
Hochberg, I. et al. Bi-allelic variants in the mitochondrial RNase P subunit PRORP cause mitochondrial tRNA processing defects and pleiotropic multisystem presentations. Am. J. Hum. Genet. 108, 2195–2204 (2021).
pubmed: 34715011
pmcid: 8595931
doi: 10.1016/j.ajhg.2021.10.002
Merante, F. et al. A biochemically distinct form of cytochrome oxidase (COX) deficiency in the Saguenay-Lac–Saint-Jean region of Quebec. Am. J. Hum. Genet. 53, 481–487 (1993).
pubmed: 8392290
pmcid: 1682348
Ghezzi, D. et al. FASTKD2 nonsense mutation in an infantile mitochondrial encephalomyopathy associated with cytochrome c oxidase deficiency. Am. J. Hum. Genet. 83, 415–423 (2008).
pubmed: 18771761
pmcid: 2556431
doi: 10.1016/j.ajhg.2008.08.009
Wilson, W. C. et al. A human mitochondrial poly(A) polymerase mutation reveals the complexities of post-transcriptional mitochondrial gene expression. Hum. Mol. Genet. 23, 6345–6355 (2014).
pubmed: 25008111
pmcid: 4222368
doi: 10.1093/hmg/ddu352
von Ameln, S. et al. A mutation in PNPT1, encoding mitochondrial-RNA-import protein PNPase, causes hereditary hearing loss. Am. J. Hum. Genet. 91, 919–927 (2012).
doi: 10.1016/j.ajhg.2012.09.002
Richter, U. et al. RNA modification landscape of the human mitochondrial tRNA
pubmed: 30262910
pmcid: 6160436
doi: 10.1038/s41467-018-06471-z
Boczonadi, V. & Horvath, R. Mitochondria: impaired mitochondrial translation in human disease. Int. J. Biochem. Cell Biol. 48, 77–84 (2014).
pubmed: 24412566
pmcid: 3988845
doi: 10.1016/j.biocel.2013.12.011
Antonicka, H., Sasarman, F., Kennaway, N. & Shoubridge, E. The molecular basis for tissue specificity of the oxidative phosphorylation deficiencies in patients with mutations in the mitochondrial translation factor EFG1. Hum. Mol. Genet. 15, 1835–1846 (2006).
pubmed: 16632485
doi: 10.1093/hmg/ddl106
Smeitink, J. et al. Distinct clinical phenotypes associated with a mutation in the mitochondrial translation elongation factor EFTs. Am. J. Hum. Genet. 79, 869–877 (2006).
pubmed: 17033963
pmcid: 1698578
doi: 10.1086/508434
Valente, L. et al. Infantile encephalopathy and defective mitochondrial DNA translation in patients with mutations of mitochondrial elongation factors EFG1 and EFTu. Am. J. Hum. Genet. 80, 44–58 (2007).
pubmed: 17160893
doi: 10.1086/510559
Weraarpachai, W. et al. Mutation in TACO1, encoding a translational activator of COX I, results in cytochrome c oxidase deficiency and late-onset Leigh syndrome. Nat. Genet. 41, 833–837 (2009).
pubmed: 19503089
doi: 10.1038/ng.390
Ferreira, N. et al. Murine cytomegalovirus infection exacerbates complex IV deficiency in a model of mitochondrial disease. PLoS Genet. 16, e1008604 (2020).
pubmed: 32130224
pmcid: 7055822
doi: 10.1371/journal.pgen.1008604
Antonicka, H. et al. Mutations in C12orf65 in patients with encephalomyopathy and a mitochondrial translation defect. Am. J. Hum. Genet. 87, 115–122 (2010).
pubmed: 20598281
pmcid: 2896764
doi: 10.1016/j.ajhg.2010.06.004
Koeck, T. et al. A common variant in TFB1M is associated with reduced insulin secretion and increased future risk of type 2 diabetes. Cell Metab. 13, 80–91 (2011).
pubmed: 21195351
doi: 10.1016/j.cmet.2010.12.007
Rossetti, G. et al. A common genetic variant of a mitochondrial RNA processing enzyme predisposes to insulin resistance. Sci. Adv. 7, eabi7514 (2021).
pubmed: 34559558
pmcid: 8462889
doi: 10.1126/sciadv.abi7514
Richman, T. R. et al. Mitochondrial mistranslation modulated by metabolic stress causes cardiovascular disease and reduced lifespan. Aging Cell 20, e13408 (2021).
pubmed: 34096683
pmcid: 8282274
doi: 10.1111/acel.13408
Inoue, K. et al. Generation of mice with mitochondrial dysfunction by introducing mouse mtDNA carrying a deletion into zygotes. Nat. Genet. 26, 176–181 (2000).
pubmed: 11017072
doi: 10.1038/82826
Stewart, J. B. Current progress with mammalian models of mitochondrial DNA disease. J. Inherit. Metab. Dis. 44, 325–342 (2021).
pubmed: 33099782
doi: 10.1002/jimd.12324
Kasahara, A. et al. Generation of trans-mitochondrial mice carrying homoplasmic mtDNAs with a missense mutation in a structural gene using ES cells. Hum. Mol. Genet. 15, 871–881 (2006).
pubmed: 16449238
doi: 10.1093/hmg/ddl005
Fan, W. et al. A mouse model of mitochondrial disease reveals germline selection against severe mtDNA mutations. Science 319, 958–962 (2008).
pubmed: 18276892
pmcid: 3049809
doi: 10.1126/science.1147786
Lin, C. S. et al. Mouse mtDNA mutant model of Leber hereditary optic neuropathy. Proc. Natl Acad. Sci. USA 109, 20065–20070 (2012).
pubmed: 23129651
pmcid: 3523873
doi: 10.1073/pnas.1217113109
Larsson, N.-G. et al. Mitochondrial transcription factor A is necessary for mtDNA maintenance and embryogenesis in mice. Nat. Genet. 18, 231–236 (1998). This paper is the first report of the in vivo role of TFAM.
pubmed: 9500544
doi: 10.1038/ng0398-231
Hance, N., Ekstrand, M. I. & Trifunovic, A. Mitochondrial DNA polymerase gamma is essential for mammalian embryogenesis. Hum. Mol. Genet. 14, 1775–1783 (2005).
pubmed: 15888483
doi: 10.1093/hmg/ddi184
Milenkovic, D. et al. TWINKLE is an essential mitochondrial helicase required for synthesis of nascent D-loop strands and complete mtDNA replication. Hum. Mol. Genet. 22, 1983–1993 (2013).
pubmed: 23393161
pmcid: 3633371
doi: 10.1093/hmg/ddt051
Tyynismaa, H. et al. Mutant mitochondrial helicase Twinkle causes multiple mtDNA deletions and a late-onset mitochondrial disease in mice. Proc. Natl Acad. Sci. USA 102, 17687–17692 (2005).
pubmed: 16301523
pmcid: 1308896
doi: 10.1073/pnas.0505551102
Trifunovic, A. et al. Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature 429, 417–423 (2004). This paper describes a revolutionary model of premature ageing that is a consequence of the accumulation of mtDNA mutations, which has formed the basis for many important studies of mitochondrial gene regulation and diseases.
pubmed: 15164064
doi: 10.1038/nature02517
Lee, C.-K., Klopp, R., Weindruch, R. & Prolla, T. Gene expression profile of aging and its retardation by caloric restriction. Science 285, 1390–1393 (1999).
pubmed: 10464095
doi: 10.1126/science.285.5432.1390
Bratic, A. et al. Complementation between polymerase- and exonuclease-deficient mitochondrial DNA polymerase mutants in genomically engineered flies. Nat. Commun. 6, 8808 (2015).
pubmed: 26554610
pmcid: 4773887
doi: 10.1038/ncomms9808
Baris, O. R. et al. Mosaic deficiency in mitochondrial oxidative metabolism promotes cardiac arrhythmia during aging. Cell Metab. 21, 667–677 (2015).
pubmed: 25955204
doi: 10.1016/j.cmet.2015.04.005
Kauppila, J. H. K. et al. A phenotype-driven approach to generate mouse models with pathogenic mtDNA mutations causing mitochondrial disease. Cell Rep. 16, 2980–2990 (2016). This study is the first to report the generation of a mouse line transmitting a heteroplasmic pathogenic mutation that models a mitochondrial disease.
pubmed: 27626666
pmcid: 5039181
doi: 10.1016/j.celrep.2016.08.037
Perks, K. L. et al. Adult-onset obesity is triggered by impaired mitochondrial gene expression. Sci. Adv. 3, e1700677 (2017).
pubmed: 28835921
pmcid: 5559209
doi: 10.1126/sciadv.1700677
Zschocke, J. HSD10 disease: clinical consequences of mutations in the HSD17B10 gene. J. Inherit. Metab. Dis. 35, 81–89 (2012).
pubmed: 22127393
doi: 10.1007/s10545-011-9415-4
Taylor, R. W. et al. Use of whole-exome sequencing to determine the genetic basis of multiple mitochondrial respiratory chain complex deficiencies. JAMA 312, 68 (2014).
pubmed: 25058219
pmcid: 6558267
doi: 10.1001/jama.2014.7184
Cuillerier, A. et al. Loss of hepatic LRPPRC alters mitochondrial bioenergetics, regulation of permeability transition and trans-membrane ROS diffusion. Hum. Mol. Genet. 26, 3186–3201 (2017).
pubmed: 28575497
pmcid: 5886084
doi: 10.1093/hmg/ddx202
Cámara, Y. Y. et al. MTERF4 regulates translation by targeting the methyltransferase NSUN4 to the mammalian mitochondrial ribosome. Cell Metab. 13, 527–539 (2011).
pubmed: 21531335
doi: 10.1016/j.cmet.2011.04.002
Dogan, S. A. et al. Tissue-specific loss of DARS2 activates stress responses independently of respiratory chain deficiency in the heart. Cell Metab. 19, 458–469 (2014).
pubmed: 24606902
doi: 10.1016/j.cmet.2014.02.004
Park, C. B. et al. MTERF3 is a negative regulator of mammalian mtDNA transcription. Cell 130, 273–285 (2007).
pubmed: 17662942
doi: 10.1016/j.cell.2007.05.046
Richman, T. R. et al. Mutation in MRPS34 compromises protein synthesis and causes mitochondrial dysfunction. PLoS Genet. 11, e1005089 (2015).
pubmed: 25816300
pmcid: 4376678
doi: 10.1371/journal.pgen.1005089
Richman, T. R. et al. Loss of the RNA-binding protein TACO1 causes late-onset mitochondrial dysfunction in mice. Nat. Commun. 7, 11884 (2016).
pubmed: 27319982
pmcid: 4915168
doi: 10.1038/ncomms11884
Hodgkinson, A. et al. High-resolution genomic analysis of human mitochondrial RNA sequence variation. Science 344, 413–415 (2014).
pubmed: 24763589
doi: 10.1126/science.1251110
Ferreira, N. et al. Stress signaling and cellular proliferation reverse the effects of mitochondrial mistranslation. EMBO J. 38, e102155 (2019).
pubmed: 31721250
pmcid: 6912024
doi: 10.15252/embj.2019102155
Akbergenov, R. et al. Mutant MRPS5 affects mitoribosomal accuracy and confers stress-related behavioral alterations. EMBO Rep. 19, e46193 (2018).
pubmed: 30237157
pmcid: 6216279
doi: 10.15252/embr.201846193
Zhao, Q. et al. A mitochondrial specific stress response in mammalian cells. EMBO J. 21, 4411–4419 (2002). The paper reports the discovery of transcription factors that are activated in response to a mitochondrial unfolded stress response.
pubmed: 12198143
pmcid: 126185
doi: 10.1093/emboj/cdf445
Wu, Z., Sainz, A. G. & Shadel, G. S. Mitochondrial DNA: cellular genotoxic stress sentinel. Trends Biochem. Sci. 46, 812–821 (2021). This comprehensive Review covers the current state of knowledge and new frontiers for discoveries in signalling responses to mtDNA release in the cytoplasm by the group that discovered this phenomenon.
pubmed: 34088564
doi: 10.1016/j.tibs.2021.05.004
Perks, K. L. et al. Reduced mitochondrial translation prevents diet-induced metabolic dysfunction but not inflammation. Aging 12, 19677–19700 (2020).
pubmed: 33024056
pmcid: 7732297
doi: 10.18632/aging.104010
Kaspar, S. et al. Adaptation to mitochondrial stress requires CHOP-directed tuning of ISR. Sci. Adv. 7, eabf0971 (2021).
pubmed: 34039602
pmcid: 8153728
doi: 10.1126/sciadv.abf0971
Richter-Dennerlein, R. et al. Mitochondrial protein synthesis adapts to influx of nuclear-encoded protein. Cell 167, 471–483.e10 (2016).
pubmed: 27693358
pmcid: 5055049
doi: 10.1016/j.cell.2016.09.003
Wang, C. et al. MITRAC15/COA1 promotes mitochondrial translation in a ND2 ribosome–nascent chain complex. EMBO Rep. 21, 1–12 (2019).
Molenaars, M. et al. A conserved mito-cytosolic translational balance links two longevity pathways. Cell Metab. 31, 549–563.e7 (2020).
pubmed: 32084377
pmcid: 7214782
doi: 10.1016/j.cmet.2020.01.011
Bonekamp, N. A. et al. Small-molecule inhibitors of human mitochondrial DNA transcription. Nature 588, 712–716 (2020).
pubmed: 33328633
doi: 10.1038/s41586-020-03048-z
Tadepalle, N. & Shadel, G. S. RNA reports breaking news from mitochondria. Mol. Cell 81, 1863–1865 (2021).
pubmed: 33961775
doi: 10.1016/j.molcel.2021.04.005
Grochowska, J., Czerwinska, J., Borowski, L. S. & Szczesny, R. J. Mitochondrial RNA, a new trigger of the innate immune system. Wiley Interdiscip. Rev. RNA 8, e1690 (2021).
West, A. P. et al. Mitochondrial DNA stress primes the antiviral innate immune response. Nature 520, 553–557 (2015). The paper was the first to report on mtDNA stress that initiates an innate immune response in cells.
pubmed: 25642965
pmcid: 4409480
doi: 10.1038/nature14156
Hensen, F. et al. Mitochondrial RNA granules are critically dependent on mtDNA replication factors Twinkle and mtSSB. Nucleic Acids Res. 47, 3680–3698 (2019).
pubmed: 30715486
pmcid: 6468249
doi: 10.1093/nar/gkz047