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Invited Review | Open Access

Multi-phase separation in mitochondrial nucleoids and eukaryotic nuclei

Qi Long1,2Yanshuang Zhou1,2Jingyi Guo1,2Hao Wu1,2Xingguo Liu1,2,3( )
CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Guangzhou Medical University; Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China
Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, China-New Zealand Joint Laboratory on Biomedicine and Health, CUHK-GIBH Joint Research Laboratory on Stem Cells and Regenerative Medicine, Institute for Stem Cell and Regeneration, Institute for Stem Cell and Regeneration, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China
Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong SAR, China

Qi Long and Yanshuang Zhou contributed equally to this work.

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Graphical Abstract

Abstract

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.

References

 

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

Biophysics Reports
Pages 113-119
Cite this article:
Long Q, Zhou Y, Guo J, et al. Multi-phase separation in mitochondrial nucleoids and eukaryotic nuclei. Biophysics Reports, 2023, 9(3): 113-119. https://doi.org/10.52601/bpr.2023.220018

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Received: 11 August 2022
Accepted: 10 February 2023
Published: 27 March 2023
© The Author(s) 2023

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