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Structure of the mitochondrial import gate reveals distinct preprotein paths.

Araiso Y, Tsutsumi A, Qiu J, Imai K, Shiota T, Song J, Lindau C, Wenz LS, Sakaue H, Yunoki K, Kawano S, Suzuki J, Wischnewski M, Schütze C, Ariyama H, Ando T, Becker T, Lithgow T, Wiedemann N, Pfanner N, Kikkawa M, Endo T
Nature 575 395-401 (2019)
Cited: 82 times
EuropePMC logo PMID: 31600774

Abstract

The translocase of the outer mitochondrial membrane (TOM) is the main entry gate for proteins1-4. Here we use cryo-electron microscopy to report the structure of the yeast TOM core complex5-9 at 3.8-Å resolution. The structure reveals the high-resolution architecture of the translocator consisting of two Tom40 β-barrel channels and α-helical transmembrane subunits, providing insight into critical features that are conserved in all eukaryotes1-3. Each Tom40 β-barrel is surrounded by small TOM subunits, and tethered by two Tom22 subunits and one phospholipid. The N-terminal extension of Tom40 forms a helix inside the channel; mutational analysis reveals its dual role in early and late steps in the biogenesis of intermembrane-space proteins in cooperation with Tom5. Each Tom40 channel possesses two precursor exit sites. Tom22, Tom40 and Tom7 guide presequence-containing preproteins to the exit in the middle of the dimer, whereas Tom5 and the Tom40 N extension guide preproteins lacking a presequence to the exit at the periphery of the dimer.

Reviews - 6jnf mentioned but not cited (3)

  1. A Biochemical and Structural Understanding of TOM Complex Interactions and Implications for Human Health and Disease. Pitt AS, Buchanan SK. Cells 10 1164 (2021)
  2. Building Better Barrels - β-barrel Biogenesis and Insertion in Bacteria and Mitochondria. Diederichs KA, Buchanan SK, Botos I. J Mol Biol 433 166894 (2021)
  3. Targeting and Insertion of Membrane Proteins in Mitochondria. Eaglesfield R, Tokatlidis K. Front Cell Dev Biol 9 803205 (2021)

Articles - 6jnf mentioned but not cited (5)



Reviews citing this publication (35)

  1. Quality control of the mitochondrial proteome. Song J, Herrmann JM, Becker T. Nat Rev Mol Cell Biol 22 54-70 (2021)
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  10. The Role of Voltage-Dependent Anion Channel in Mitochondrial Dysfunction and Human Disease. Varughese JT, Buchanan SK, Pitt AS. Cells 10 1737 (2021)
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  14. Mechanisms of Non-Vesicular Exchange of Lipids at Membrane Contact Sites: Of Shuttles, Tunnels and, Funnels. Egea PF. Front Cell Dev Biol 9 784367 (2021)
  15. Tim17 Updates: A Comprehensive Review of an Ancient Mitochondrial Protein Translocator. Chaudhuri M, Darden C, Gonzalez FS, Singha UK, Quinones L, Tripathi A. Biomolecules 10 E1643 (2020)
  16. Tools for the Recognition of Sorting Signals and the Prediction of Subcellular Localization of Proteins From Their Amino Acid Sequences. Imai K, Nakai K. Front Genet 11 607812 (2020)
  17. Protein Quality Control at the Mitochondrial Surface. den Brave F, Gupta A, Becker T. Front Cell Dev Biol 9 795685 (2021)
  18. Cytosolic Quality Control of Mitochondrial Protein Precursors-The Early Stages of the Organelle Biogenesis. Lenkiewicz AM, Krakowczyk M, Bragoszewski P. Int J Mol Sci 23 7 (2021)
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  21. Altered Mitochondrial Protein Homeostasis and Proteinopathies. Jishi A, Qi X. Front Mol Neurosci 15 867935 (2022)
  22. Voltage-Dependent Anion Selective Channel 3: Unraveling Structural and Functional Features of the Least Known Porin Isoform. Reina S, Checchetto V. Front Physiol 12 784867 (2021)
  23. Alcohol-Induced Neuroinflammatory Response and Mitochondrial Dysfunction on Aging and Alzheimer's Disease. León BE, Kang S, Franca-Solomon G, Shang P, Choi DS. Front Behav Neurosci 15 778456 (2021)
  24. Coordinated Translocation of Presequence-Containing Precursor Proteins Across Two Mitochondrial Membranes: Knowns and Unknowns of How TOM and TIM23 Complexes Cooperate With Each Other. Genge MG, Mokranjac D. Front Physiol 12 806426 (2021)
  25. The Biogenesis Process of VDAC - From Early Cytosolic Events to Its Final Membrane Integration. Moitra A, Rapaport D. Front Physiol 12 732742 (2021)
  26. Crosstalk between Mitochondrial Protein Import and Lipids. Hoffmann JJ, Becker T. Int J Mol Sci 23 5274 (2022)
  27. Post-transcriptional control of mitochondrial protein composition in changing environmental conditions. Tsuboi T, Leff J, Zid BM. Biochem Soc Trans 48 2565-2578 (2020)
  28. Role of Hsp70 in Post-Translational Protein Targeting: Tail-Anchored Membrane Proteins and Beyond. Shan SO. Int J Mol Sci 24 1170 (2023)
  29. The Diversity of the Mitochondrial Outer Membrane Protein Import Channels: Emerging Targets for Modulation. Mazur M, Kmita H, Wojtkowska M. Molecules 26 4087 (2021)
  30. Spatiotemporal resolution in high-speed atomic force microscopy for studying biological macromolecules in action. Umeda K, McArthur SJ, Kodera N. Microscopy (Oxf) 72 151-161 (2023)
  31. Dissecting the molecular mechanisms of mitochondrial import and maturation of peroxiredoxins from yeast and mammalian cells. Gomes F, Turano H, Ramos A, de Barros MH, Haddad LA, Netto LES. Biophys Rev 13 983-994 (2021)
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Articles citing this publication (39)



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