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In mammalian cells, besides nuclei, mitochondria are the only semi-autonomous organelles possessing own DNA organized in the form of nucleoids. While eukaryotic nuclear DNA compaction, chromatin compartmentalization and transcription are regulated by phase separation, our recent work proposed a model of mitochondrial nucleoid self-assembly and transcriptional regulation by multi-phase separation. Herein, we summarized the phase separation both in the nucleus and mitochondrial nucleoids, and did a comparison of the organization and activity regulating, which would provide new insight into the understanding of both architecture and genetics of nucleus and mitochondrial nucleoids.
Alberti S, Gladfelter A, Mittag T (2019) Considerations and challenges in studying liquid-liquid phase separation and biomolecular condensates. Cell 176(3): 419−434
Banani SF, Lee HO, Hyman AA, Rosen MK (2017) Biomolecular condensates: organizers of cellular biochemistry. Nat Rev Mol Cell Biol 18(5): 285−298
Banani SF, Rice AM, Peeples WB, Lin Y, Jain S, Parker R, Rosen MK (2016) Compositional control of phase-separated cellular bodies. Cell 166(3): 651−663
Bi X, Xu Y, Li T, Li X, Li W, Shao W, Wang K, Zhan G, Wu Z, Liu W, Lu JY, Wang L, Zhao J, Wu J, Na J, Li G, Li P, Shen X (2019) RNA targets ribogenesis factor WDR43 to chromatin for transcription and pluripotency control. Mol Cell 75(1): 102−116
Boehning M, Dugast-Darzacq C, Rankovic M, Hansen AS, Yu T, Marie-Nelly H, McSwiggen DT, Kokic G, Dailey GM, Cramer P, Darzacq X, Zweckstetter M (2018) RNA polymerase II clustering through carboxy-terminal domain phase separation. Nat Struct Mol Biol 25(9): 833−840
Boeynaems S, Alberti S, Fawzi NL, Mittag T, Polymenidou M, Rousseau F, Schymkowitz J, Shorter J, Wolozin B, Van Den Bosch L, Tompa P, Fuxreiter M (2018) Protein phase separation: a new phase in cell biology. Trends Cell Biol 28(6): 420−435
Brangwynne CP, Mitchison TJ, Hyman AA (2011) Active liquid-like behavior of nucleoli determines their size and shape in Xenopus laevis oocytes. Proc Natl Acad Sci USA 108(11): 4334−4339
Cheng Y, Xie W, Pickering BF, Chu KL, Savino AM, Yang X, Luo H, Nguyen DT, Mo S, Barin E, Velleca A, Rohwetter TM, Patel DJ, Jaffrey SR, Kharas MG (2021) N(6)-Methyladenosine on mRNA facilitates a phase-separated nuclear body that suppresses myeloid leukemic differentiation. Cancer Cell 39(7): 958−972
Cho WK, Spille JH, Hecht M, Lee C, Li C, Grube V, Cisse, II (2018) Mediator and RNA polymerase II clusters associate in transcription-dependent condensates. Science 361(6400): 412−415
Cogliati S, Frezza C, Soriano ME, Varanita T, Quintana-Cabrera R, Corrado M, Cipolat S, Costa V, Casarin A, Gomes LC, Perales-Clemente E, Salviati L, Fernandez-Silva P, Enriquez JA, Scorrano L (2013) Mitochondrial cristae shape determines respiratory chain supercomplexes assembly and respiratory efficiency. Cell 155(1): 160−171
Durniak KJ, Bailey S, Steitz TA (2008) The structure of a transcribing T7 RNA polymerase in transition from initiation to elongation. Science 322(5901): 553−557
Farge G, Mehmedovic M, Baclayon M, van den Wildenberg SM, Roos WH, Gustafsson CM, Wuite GJ, Falkenberg M (2014) In vitro-reconstituted nucleoids can block mitochondrial DNA replication and transcription. Cell Rep 8(1): 66−74
Feric M, Demarest TG, Tian J, Croteau DL, Bohr VA, Misteli T (2021) Self-assembly of multi-component mitochondrial nucleoids via phase separation. EMBO J 40(6): e107165. https://doi.org/10.15252/embj.2020107165
Feric M, Vaidya N, Harmon TS, Mitrea DM, Zhu L, Richardson TM, Kriwacki RW, Pappu RV, Brangwynne CP (2016) Coexisting liquid phases underlie nucleolar subcompartments. Cell 165(7): 1686−1697
Frey TG, Mannella CA (2000) The internal structure of mitochondria. Trends Biochem Sci 25(7): 319−324
Guo YE, Manteiga JC, Henninger JE, Sabari BR, Dall'Agnese A, Hannett NM, Spille JH, Afeyan LK, Zamudio AV, Shrinivas K, Abraham BJ, Boija A, Decker TM, Rimel JK, Fant CB, Lee TI, Cisse, II, Sharp PA, Taatjes DJ, Young RA (2019) Pol II phosphorylation regulates a switch between transcriptional and splicing condensates. Nature 572(7770): 543−548
Gustafsson CM, Falkenberg M, Larsson NG (2016) Maintenance and expression of mammalian mitochondrial DNA. Annu Rev Biochem 85: 133−160
Hansen AS, Hsieh TS, Cattoglio C, Pustova I, Saldana-Meyer R, Reinberg D, Darzacq X, Tjian R (2019) Distinct classes of chromatin loops revealed by deletion of an RNA-binding region in CTCF. Mol Cell 76(3): 395−411
Henninger JE, Oksuz O, Shrinivas K, Sagi I, LeRoy G, Zheng MM, Andrews JO, Zamudio AV, Lazaris C, Hannett NM, Lee TI, Sharp PA, Cisse, II, Chakraborty AK, Young RA (2020) RNA-mediated feedback control of transcriptional condensates. Cell 184(1): 207−225
Hillen HS, Morozov YI, Sarfallah A, Temiakov D, Cramer P (2017) Structural basis of mitochondrial transcription initiation. Cell 171(5): 1072−1081
Hillen HS, Temiakov D, Cramer P (2018) Structural basis of mitochondrial transcription. Nat Struct Mol Biol 25(9): 754−765
Jourdain AA, Koppen M, Wydro M, Rodley CD, Lightowlers RN, Chrzanowska-Lightowlers ZM, Martinou JC (2013) GRSF1 regulates RNA processing in mitochondrial RNA granules. Cell Metab 17(3): 399−410
Klein IA, Boija A, Afeyan LK, Hawken SW, Fan M, Dall'Agnese A, Oksuz O, Henninger JE, Shrinivas K, Sabari BR, Sagi I, Clark VE, Platt JM, Kar M, McCall PM, Zamudio AV, Manteiga JC, Coffey EL, Li CH, Hannett NM, Guo YE, Decker TM, Lee TI, Zhang T, Weng JK, Taatjes DJ, Chakraborty A, Sharp PA, Chang YT, Hyman AA, Gray NS, Young RA (2020) Partitioning of cancer therapeutics in nuclear condensates. Science 368(6497): 1386−1392
Kukat C, Davies KM, Wurm CA, Spåhr H, Bonekamp NA, Kühl I, Joos F, Polosa PL, Park CB, Posse V, Falkenberg M, Jakobs S, Kühlbrandt W, Larsson NG (2015) Cross-strand binding of TFAM to a single mtDNA molecule forms the mitochondrial nucleoid. Proc Natl Acad Sci USA 112(36): 11288−11293
Ladouceur AM, Parmar BS, Biedzinski S, Wall J, Tope SG, Cohn D, Kim A, Soubry N, Reyes-Lamothe R, Weber SC (2020) Clusters of bacterial RNA polymerase are biomolecular condensates that assemble through liquid-liquid phase separation. Proc Natl Acad Sci USA 117(31): 18540−18549
Lafontaine DLJ, Riback JA, Bascetin R, Brangwynne CP (2021) The nucleolus as a multiphase liquid condensate. Nat Rev Mol Cell Biol 22(3): 165−182
Larson AG, Elnatan D, Keenen MM, Trnka MJ, Johnston JB, Burlingame AL, Agard DA, Redding S, Narlikar GJ (2017) Liquid droplet formation by HP1alpha suggests a role for phase separation in heterochromatin. Nature 547(7662): 236−240
Larson AG, Narlikar GJ (2018) The role of phase separation in heterochromatin formation, function, and regulation. Biochemistry 57(17): 2540−2548
Lee JH, Wang R, Xiong F, Krakowiak J, Liao Z, Nguyen PT, Moroz-Omori EV, Shao J, Zhu X, Bolt MJ, Wu H, Singh PK, Bi M, Shi CJ, Jamal N, Li G, Mistry R, Jung SY, Tsai KL, Ferreon JC, Stossi F, Caflisch A, Liu Z, Mancini MA, Li W (2021) Enhancer RNA m6A methylation facilitates transcriptional condensate formation and gene activation. Mol Cell 81(16): 3368−3385
Long Q, Zhou Y, Wu H, Du S, Hu M, Qi J, Li W, Guo J, Wu Y, Yang L, Xiang G, Wang L, Ye S, Wen J, Mao H, Wang J, Zhao H, Chan WY, Liu J, Chen Y, Li P, Liu X (2021) Phase separation drives the self-assembly of mitochondrial nucleoids for transcriptional modulation. Nat Struct Mol Biol 28(11): 900−908
Lu H, Yu D, Hansen AS, Ganguly S, Liu R, Heckert A, Darzacq X, Zhou Q (2018) Phase-separation mechanism for C-terminal hyperphosphorylation of RNA polymerase II. Nature 558(7709): 318−323
Masters BS, Stohl LL, Clayton DA (1987) Yeast mitochondrial RNA polymerase is homologous to those encoded by bacteriophages T3 and T7. Cell 51(1): 89−99
Misteli T (2020) The self-organizing genome: principles of genome architecture and function. Cell 183(1): 28−45
Nava MM, Miroshnikova YA, Biggs LC, Whitefield DB, Metge F, Boucas J, Vihinen H, Jokitalo E, Li X, Garcia Arcos JM, Hoffmann B, Merkel R, Niessen CM, Dahl KN, Wickstrom SA (2020) Heterochromatin-driven nuclear softening protects the genome against mechanical stress-induced damage. Cell 181(4): 800−817
Ngo HB, Lovely GA, Phillips R, Chan DC (2014) Distinct structural features of TFAM drive mitochondrial DNA packaging versus transcriptional activation. Nat Commun 5: 3077. https://doi.org/10.1038/ncomms4077
Pearce SF, Rebelo-Guiomar P, D'Souza AR, Powell CA, Van Haute L, Minczuk M (2017) Regulation of mammalian mitochondrial gene expression: recent advances. Trends Biochem Sci 42(8): 625−639
Riback JA, Zhu L, Ferrolino MC, Tolbert M, Mitrea DM, Sanders DW, Wei M-T, Kriwacki RW, Brangwynne CP (2020) Composition-dependent thermodynamics of intracellular phase separation. Nature 581(7807): 209−214
Roger AJ, Munoz-Gomez SA, Kamikawa R (2017) The origin and diversification of mitochondria. Curr Biol 27(21): R1177−R1192
Sabari BR, Dall'Agnese A, Boija A, Klein IA, Coffey EL, Shrinivas K, Abraham BJ, Hannett NM, Zamudio AV, Manteiga JC, Li CH, Guo YE, Day DS, Schuijers J, Vasile E, Malik S, Hnisz D, Lee TI, Cisse, II, Roeder RG, Sharp PA, Chakraborty AK, Young RA (2018) Coactivator condensation at super-enhancers links phase separation and gene control. Science 361(6400): eaar3958. https://doi.org/10.1126/science.aar3958
Sabari BR, Dall'Agnese A, Young RA (2020) Biomolecular condensates in the nucleus. Trends Biochem Sci 45(11): 961−977
Shen EL, Bogenhagen DF (2001) Developmentally-regulated packaging of mitochondrial DNA by the HMG-box protein mtTFA during Xenopus oogenesis. Nucleic Acids Res 29(13): 2822−2828
Shin Y, Brangwynne CP (2017) Liquid phase condensation in cell physiology and disease. Science 357(6357): eaaf4382. https://doi.org/10.1126/science.aaf4382
Song F, Chen P, Sun D, Wang M, Dong L, Liang D, Xu RM, Zhu P, Li G (2014) Cryo-EM study of the chromatin fiber reveals a double helix twisted by tetranucleosomal units. Science 344(6182): 376−380
Steinbach N, Hasson D, Mathur D, Stratikopoulos EE, Sachidanandam R, Bernstein E, Parsons RE (2019) PTEN interacts with the transcription machinery on chromatin and regulates RNA polymerase II-mediated transcription. Nucleic Acids Res 47(11): 5573−5586
Strickfaden H, Tolsma TO, Sharma A, Underhill DA, Hansen JC, Hendzel MJ (2020) Condensed chromatin behaves like a solid on the mesoscale in vitro and in living cells. Cell 183(7): 1772−1784
Strom AR, Emelyanov AV, Mir M, Fyodorov DV, Darzacq X, Karpen GH (2017) Phase separation drives heterochromatin domain formation. Nature 547(7662): 241−245
Takamatsu C, Umeda S, Ohsato T, Ohno T, Abe Y, Fukuoh A, Shinagawa H, Hamasaki N, Kang D (2002) Regulation of mitochondrial D-loops by transcription factor A and single-stranded DNA-binding protein. EMBO Rep 3(5): 451−456
Terzioglu M, Ruzzenente B, Harmel J, Mourier A, Jemt E, Lopez MD, Kukat C, Stewart JB, Wibom R, Meharg C, Habermann B, Falkenberg M, Gustafsson CM, Park CB, Larsson NG (2013) MTERF1 binds mtDNA to prevent transcriptional interference at the light-strand promoter but is dispensable for rRNA gene transcription regulation. Cell Metab 17(4): 618−626
Wang J, Choi JM, Holehouse AS, Lee HO, Zhang X, Jahnel M, Maharana S, Lemaitre R, Pozniakovsky A, Drechsel D, Poser I, Pappu RV, Alberti S, Hyman AA (2018) A molecular grammar governing the driving forces for phase separation of prion-like RNA binding proteins. Cell 174(3): 688−699
Wang L, Hu M, Zuo MQ, Zhao J, Wu D, Huang L, Wen Y, Li Y, Chen P, Bao X, Dong MQ, Li G, Li P (2020) Rett syndrome-causing mutations compromise MeCP2-mediated liquid-liquid phase separation of chromatin. Cell Res 30(5): 393−407
Yakubovskaya E, Mejia E, Byrnes J, Hambardjieva E, Garcia-Diaz M (2010) Helix unwinding and base flipping enable human MTERF1 to terminate mitochondrial transcription. Cell 141(6): 982−993
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