CoChat
Sign Up
PreprintCited by 96Mitochondrial Function and PathologyAdvanced Electron Microscopy Techniques and ApplicationsATP Synthase and ATPases Research

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

In-cell architecture of the mitochondrial respiratory chain

Open access
Waltz, Florent, Righetto, Ricardo D., Kelley, Ron, Zhang, Xianjun, Obr, Martin, Khavnekar, Sagar, Kotecha, Abhay, Engel, Benjamin D.·2024·Science
DOI 10.1101/2024.09.03.610704

Preprint — published as 10.1126/science.ads8738 · Paper page

Open this paper in CoChat — free account

Abstract

Mitochondria produce energy through oxidative phosphorylation, carried out by five membrane-bound complexes collectively known as the respiratory chain. These complexes work in concert to transfer electrons and pump protons, leading to ATP regeneration. The precise organization of these complexes in native cells is debated, notably their assembly into higher-order supercomplexes called respirasomes. Here, we use in situ cryo-electron tomography to visualize the native structures and organization of several major mitochondrial complexes inside Chlamydomonas reinhardtii cells. ATP synthases and respiratory complexes are segregated into curved and flat crista membrane domains, respectively. Respiratory complexes I, III, and IV assemble into a single type of respirasome, from which we determined a native 5 Å-resolution structure showing the binding of electron carrier cytochrome c . Combined with single-particle cryo-electron microscopy reconstruction at 2.4 Å resolution, we assemble a detailed model of how the respiratory complexes interact with each other inside native mitochondria.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1101/2024.09.03.610704

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 94

  1. 2012, Mitochondrial Evolution, Cold SpringHarbor Perspectivesin Biology, 4, a011403
  2. 10.1038/191144a0 · DOI · Paper page
  3. J. S. Sousa , E. D’Imprima , J. Vonck , “Mitochondrial Respiratory Chain Complexes” (2018; http://link.springer.com/10.1007/978-981-10-7757-9_7), pp. 167–227. · DOI
  4. A. Mühleip , S.E. McComas , A. Amunts , Structure of a mitochondrial ATPsynthasewith bound native cardiolipin. eLife 8 (2019). · DOI
  5. A. Mühleip , R. Kock Flygaard , J. Ovciarikova , A. Lacombe , P. Fernandes , L. Sheiner , A. Amunts , ATPsynthase hexamer assemblies shape cristae of Toxoplasma mitochondria. Nat Commun 12, 120 (2021). · DOI
  6. 10.1038/s41467-020-18993-6 · DOI
  7. 2020, Structure of the dimeric ATP synthase from bovine mitochondria, Proceedingsof the National Academy of Sciencesof the United States of America, 117, 23519, 10.1073/pnas.2013998117 · DOI
  8. 10.1016/j.sbi.2020.01.004 · DOI
  9. 2022, Structures of Tetrahymena’s respiratory chain reveal the diversity of eukaryotic core metabolism, Science, 376, 831, 10.1126/science.abn7747 · DOI
  10. 2021, Aferredoxin bridge connects the two arms of plant mitochondrial complex I, ThePlant Cell, 33, 2072, 10.1093/plcell/koab092 · DOI
  11. 10.1016/j.cub.2020.02.053 · DOI
  12. I. Vercellino , L. A. Sazanov , SCAF1 drives the compositional diversity of mammalian respirasomes. Nat Struct Mol Biol, 1–11 (2024). · DOI
  13. 10.1038/nature19359 · DOI
  14. 10.1038/nature19774 · DOI · Paper page
  15. 10.1016/j.cell.2016.11.012 · DOI
  16. 2024, Euglena’s atypical respiratory chain adapts to the discoidal cristae and flexible metabolism, Nat Commun, 15, 1628, 10.1038/s41467-024-46018-z · DOI
  17. 10.1038/s41586-023-05817-y · DOI
  18. 2023, Cryo-EMstructure of the respiratory I + III2supercomplex from Arabidopsisthaliana at 2 Åresolution, Nat Plants, 9, 142
  19. 10.7554/eLife.62047 · DOI
  20. 2023, Plant-specific features of respiratory supercomplex I + III2 from Vigna radiata, Nat. Plants, 9, 157
  21. 10.1101/2024.05.25.595893 · DOI
  22. 10.1038/s41594-018-0172-z · DOI
  23. 2019, Structure and Mechanisms of F-Type ATP Synthases, Annual Review of Biochemistry, 88, 515, 10.1146/annurev-biochem-013118-110903 · DOI
  24. 2001, The Ratio of Oxidative Phosphorylation Complexes I–V in Bovine Heart Mitochondria and the Composition of Respiratory Chain Supercomplexes*, Journalof Biological Chemistry, 276, 37861, 10.1074/jbc.M106474200 · DOI
  25. 10.1104/pp.103.038018 · DOI
  26. 10.1104/pp.103.024620 · DOI
  27. 10.1093/emboj/19.8.1777 · DOI · Paper page
  28. 10.1016/j.cell.2024.01.005 · DOI
  29. 10.1038/s41586-024-07198-2 · DOI
  30. 10.1038/s41586-023-06690-5 · DOI
  31. H. Xing , R. Taniguchi , I. Khusainov , J.P. Kreysing , S. Welsch , B. Turoňová , M. Beck , Translation dynamics in human cells visualizedat highresolution revealcancer drugaction. Scienc e 381 , 70–75 (2023). · DOI
  32. 10.1038/s41586-022-05255-2 · DOI · Paper page
  33. M. Schaffer , B. Engel , T. Laugks , J. Mahamid , J. Plitzko , W. Baumeister , Cryo-focused Ion Beam Sample Preparation for Imaging Vitreous Cells by Cryo-electron Tomography. BIO-PROTOCOL 5 (2015). · DOI
  34. 10.1146/annurev-biophys-111622-091327 · DOI
  35. 2023, Chlamydomonas reinhardtii: a model for photosynthesis and so much more, Nature Methods, 20, 1441, 10.1038/s41592-023-02023-6 · DOI
  36. 2022, In situ architecture of the ciliary base reveals the stepwise assembly of intraflagellar transport trains. Science (New York, N.Y, 377, 543, 10.1126/science.abm6704 · DOI
  37. 2022, Ciliary central apparatus structure reveals mechanisms of microtubule patterning, Nat Struct Mol Biol, 29, 483, 10.1038/s41594-022-00770-2 · DOI
  38. 2021, How to build a ribosome from RNAfragments in Chlamydomonas mitochondria, Nature Communications, 12, 7176, 10.1038/s41467-021-27200-z · DOI
  39. 10.1104/pp.104.054148 · DOI
  40. 10.1101/2024.03.25.586705 · DOI
  41. 2023, Mitochondrial Cristae Morphology Reflecting Metabolism, Superoxide Formation, Redox Homeostasis, and Pathology, Antioxid Redox Signal, 39, 635, 10.1089/ars.2022.0173 · DOI
  42. 2018, Three-Dimensional Analysis of Mitochondrial Crista Ultrastructure in a Patient with Leigh Syndromeby In Situ Cryoelectron Tomography. iScience, 6, 83–91
  43. 2023, Quantifying organellar ultrastructure in cryo-electron tomographyusing a surface morphometrics pipeline, Journal of Cell Biology, 222, e202204093, 10.1083/jcb.202204093 · DOI · Paper page
  44. 10.1101/2024.02.14.579514 · DOI
  45. 10.1101/2024.03.27.586927 · DOI
  46. 2024, Theconsequence of ATPsynthase dimer angle on mitochondrial morphology studied by cryo-electron tomography, Biochemical Journal, 481, 161, 10.1042/BCJ20230450 · DOI
  47. 10.1073/pnas.1204593109 · DOI · Paper page
  48. 2015, Organization of the mitochondrial translation machinery studied in situ by cryoelectron tomography, Nature Communications, 6, 6019, 10.1038/ncomms7019 · DOI
  49. 10.1016/j.str.2017.07.011 · DOI
  50. 1997, Mitochondrial biogenesis: TheTom and Tim machine. Current Biology, 7, R100
  51. W. Zheng , P. Chai , J. Zhu , K. Zhang , High-resolution in situ structures of mammalian respiratory supercomplexes. Nature, 1–8 (2024). · DOI
  52. 2018, Conservedin situ arrangement of complex I and III2 in mitochondrial respiratory chain supercomplexes of mammals, yeast, and plants, Proceedingsof the National Academyof Sciencesof the United Statesof America, 115, 3024, 10.1073/pnas.1720702115 · DOI
  53. 2024, Promotion of oxidative phosphorylation by complex I-anchored carbonic anhydrases?, Trends in Plant Science, 29, 64, 10.1016/j.tplants.2023.07.007 · DOI
  54. 2020, Specific features and assembly of the plant mitochondrial complex I revealed by cryo-EM, Nature Communications, 11, 5195, 10.1038/s41467-020-18814-w · DOI
  55. 2019, Structures of Respiratory Supercomplex I+III2 Reveal Functional and Conformational Crosstalk, Molecular Cell, 75, 1131, 10.1016/j.molcel.2019.07.022 · DOI
  56. 2017, Complex structure of cytochrome c–cytochrome c oxidase reveals a novel protein–protein interaction mode, The EMBOJournal, 36, 291
  57. 2008, Structure of Complex III with Bound Cytochrome c in Reduced State and Definition of a Minimal Core Interface for Electron Transfer*, Journalof Biological Chemistry, 283, 17542, 10.1074/jbc.M710126200 · DOI
  58. 2023, The functional significance of mitochondrial respiratory chain supercomplexes, EMBOreports, 24, e57092
  59. 2017, Clarifying the supercomplex: the higher-order organization of the mitochondrial electron transport chain, Nature Structural & Molecular Biology, 24, 800, 10.1038/nsmb.3460 · DOI
  60. J. S. Sousa , D. J. Mills , J. Vonck , W. Kühlbrandt , Functional asymmetry and electron flow in the bovine respirasome. eLife 5 (2016). · DOI
  61. 10.1128/MCB.01767-05 · DOI
  62. 10.1126/science.1230381 · DOI · Paper page
  63. 2018, Mitochondrial Supercomplexes Do Not Enhance Catalysis by Quinone Channeling, Cell Metabolism, 28, 525, 10.1016/j.cmet.2018.05.024 · DOI
  64. 2014, Structures of mitochondrial oxidative phosphorylation supercomplexes and mechanisms for their stabilisation, Biochimica et Biophysica Acta (BBA)-Bioenergetics, 1837, 418, 10.1016/j.bbabio.2013.10.004 · DOI
  65. 10.1101/2024.07.13.602826 · DOI
  66. 2023, Preserved respiratory chain capacity and physiology in mice with profoundly reduced levels of mitochondrial respirasomes, Cell Metabolism, 35, 1799, 10.1016/j.cmet.2023.07.015 · DOI · Paper page
  67. M. Brischigliaro , A. Cabrera-Orefice , S. Arnold , C. Viscomi , M. Zeviani , E. Fernández-Vizarra , Structural rather than catalytic role for mitochondrial respiratory chain supercomplexes. eLife 12 (2023). · DOI
  68. A. Rycovska,V. Zickermann, W. Kuhlbrandt, 2011, Macromolecular organization of ATP synthase and complex I in whole mitochondria, Proceedingsof the National Academyof Sciences, 108, 14121, 10.1073/pnas.1103621108 · DOI
  69. W. Wietrzynski , M. Schaffer , D. Tegunov , S. Albert , A. Kanazawa , J.M. Plitzko , W. Baumeister , B. D. Engel , Charting the native architecture of chlamydomonas thylakoid membranes with single-molecule precision. eLife 9 (2020). · DOI
  70. 2022, The coupling mechanism of mammalian mitochondrial complex I, Nat Struct Mol Biol, 29, 172, 10.1038/s41594-022-00722-w · DOI
  71. 2022, A universal coupling mechanism of respiratory complex I, Nature, 609, 808, 10.1038/s41586-022-05199-7 · DOI
  72. D. Kampjut , L. A. Sazanov , The coupling mechanism of mammalian respiratory complex I. Science 370, eabc4209 (2020). · DOI
  73. K. Parey , J. Lasham , D. J. Mills , A. Djurabekova , O. Haapanen , E. G. Yoga , H. Xie , W. Kühlbrandt , V. Sharma , J. Vonck , V. Zickermann , High-resolution structure and dynamics of mitochondrial complex I—Insightsinto the proton pumping mechanism. Science Advances 7, eabj3221 (2021). · DOI
  74. 10.1101/2024.05.02.589639 · DOI
  75. 2017, MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy, Nature Methods, 14, 331, 10.1038/nmeth.4193 · DOI
  76. 2015, CTFFIND4:Fast and accurate defocus estimation from electron micrographs, Journalof Structural Biology, 192, 216, 10.1016/j.jsb.2015.08.008 · DOI
  77. S. Zheng , G. Wolff , G. Greenan , Z. Chen , F. G. A. Faas , M. Bárcena , A. J. Koster , Y. Cheng , D. A. Agard , AreTomo: An integrated software package for automated marker-free, motion-corrected cryo-electron tomographic alignment and reconstruction. Journal of Structural Biology: X 6, 100068 (2022). · DOI
  78. 2017, Efficient 3D-CTFcorrection for cryo-electron tomography using NovaCTFimproves subtomogram averagingresolution to 3.4 Å, Journalof Structural Biology, 199, 187, 10.1016/j.jsb.2017.07.007 · DOI
  79. T. O. Buchholz , M. Jordan , G. Pigino , F. Jug ,Cryo-CARE:Content-Aware ImageRestoration for Cryo-Transmission Electron Microscopy Data. Proceedings - International Symposium on Biomedical Imaging 2019-April, 502–506(2018). · DOI
  80. W. Wan , S. Khavnekar , J. Wagner , STOPGAP: anopen-source packagefor template matching, subtomogram alignment and classification. Acta Cryst D 80 (2024). · DOI
  81. 2012, PyTom: A python-based toolbox for localization of macromolecules in cryo-electron tomograms and subtomogram analysis, Journalof Structural Biology, 178, 177, 10.1016/j.jsb.2011.12.003 · DOI
  82. M. L. Chaillet , G. van der Schot , I. Gubins , S. Roet , R. C. Veltkamp , F. Förster , Extensive Angular Sampling Enables the Sensitive Localization of Macromolecules in Electron Tomograms. International Journalof Molecular Sciences 24, 13375 (2023). · DOI
  83. 2022, A Bayesian approach to single-particle electron cryo-tomography in RELION-4.0, eLife, 11, e83724, 10.7554/eLife.83724 · DOI
  84. 10.1038/ncomms9843 · DOI
  85. 2017, cryoSPARC: algorithms for rapid unsupervised cryo-EMstructure determination, Nature Methods, 14, 290, 10.1038/nmeth.4169 · DOI · Paper page
  86. K. Jamali , L. Käll , R. Zhang , A. Brown , D. Kimanius , S. H. W. Scheres , Automated model building and protein identification in cryo-EMmaps. Nature, 1–8(2024). · DOI · Paper page
  87. 10.1093/nar/25.17.3389 · DOI · Paper page
  88. 10.1002/PRO.4792 · DOI
  89. 2010, Features and development of Coot. Acta Crystallographica Section DBiological Crystallography, 66, 486, 10.1107/S0907444910007493 · DOI · Paper page
  90. 2019, Macromolecular structure determination using X-rays, neutrons and electrons: recent developments in Phenix, Acta Crystallographica Section DStructural Biology, 75, 861, 10.1107/S2059798319011471 · DOI · Paper page
  91. 10.1002/pro.3330 · DOI · Paper page
  92. 10.1101/2024.01.05.574336 · DOI
  93. 10.1002/pro.3235 · DOI · Paper page
  94. 2022, ArtiaX: An electron tomography toolbox for the interactive handling of sub-tomograms in UCSFChimeraX, Protein Sci, 31, e4472, 10.1002/pro.4472 · DOI

Metadata

Authors
Waltz, F., Righetto, R. D., Kelley, R., Zhang, X., Obr, M., Khavnekar, S., Kotecha, A., & Engel, B. D.
Affiliations
  • University of Basel (CH)
  • Thermo Fisher Scientific (Netherlands) (NL)
  • St. Jude Children's Research Hospital (US)
Corresponding author
  • Waltz, Florent
  • Engel, Benjamin D.
ORCID
Venue
Science
Publisher
openRxiv
Published
2024-09-04
Volume
387
Issue
6740
Pages
1296-1301
ISSN
0036-8075 (ISSN-L)
DOI
10.1101/2024.09.03.610704
OpenAlex
W4408704214
Cited by
96
References
1
Citations by year
2026: 60 · 2025: 34 · 2024: 2
FWCI
28.10
Type
journal article
Language
en
Open access
Licence
Locations
  • Science (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
  • univOAK (4 institutions : Université de Strasbourg, Université de Haute Alsace, INSA Strasbourg, Bibliothèque Nationale et Universitaire de Strasbourg) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Advanced Electron Microscopy Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
Keywords
mitochondrial respiratory chain, respirasome, respiratory chain supercomplexes, mitochondrial complex I, mitochondrial complex III, mitochondrial complex IV, ATP synthase, cytochrome c binding, oxidative phosphorylation, Chlamydomonas reinhardtii, electron transfer
MeSH terms
Protein Domains, Adenosine Triphosphate, Electron Transport Complex IV, Electron Transport, Mitochondria, Oxidative Phosphorylation, Electron Transport Complex III, Chlamydomonas reinhardtii, Cryoelectron Microscopy, Electron Transport Complex I, Cytochromes c, Mitochondrial Membranes, Electron Microscope Tomography

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review