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The biogenesis of mitochondrial intermembrane space proteins

  • Ruairidh Edwards , Sarah Gerlich and Kostas Tokatlidis ORCID logo EMAIL logo
Published/Copyright: March 12, 2020

Abstract

The mitochondrial intermembrane space (IMS) houses a large spectrum of proteins with distinct and critical functions. Protein import into this mitochondrial sub-compartment is underpinned by an intriguing variety of pathways, many of which are still poorly understood. The constricted volume of the IMS and the topological segregation by the inner membrane cristae into a bulk area surrounded by the boundary inner membrane and the lumen within the cristae is an important factor that adds to the complexity of the protein import, folding and assembly processes. We discuss the main import pathways into the IMS, but also how IMS proteins are degraded or even retro-translocated to the cytosol in an integrated network of interactions that is necessary to maintain a healthy balance of IMS proteins under physiological and cellular stress conditions. We conclude this review by highlighting new and exciting perspectives in this area with a view to develop a better understanding of yet unknown, likely unconventional import pathways, how presequence-less proteins can be targeted and the basis for dual localisation in the IMS and the cytosol. Such knowledge is critical to understanding the dynamic changes of the IMS proteome in response to stress, and particularly important for maintaining optimal mitochondrial fitness.

Acknowledgements

Work in K.T. lab is supported by UKRI-BBSRC (grants BB/R009031/1 and BB/T003804/1, Funder Id: http://dx.doi.org/10.13039/501100000268) and EU COST Action CA15133 (‘FeSBioNet’). R.E. is supported by a Lord Kelvin-Adam Smith PhD studentship (University of Glasgow) and by a BBSRC-EPSRC Impact Accelerator grant (University of Glasgow) awarded to K.T. S.G. is supported by an ERASMUS+ studentship.

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Received: 2020-01-20
Accepted: 2020-02-13
Published Online: 2020-03-12
Published in Print: 2020-05-26

©2020 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Highlight: In Honor of Walter Neupert: Mitochondria
  3. Editorial
  4. Mitochondria and friends – a special issue in honor of Walter Neupert (1939–2019)
  5. Early steps in mitochondrial protein translocation
  6. From cytosol to mitochondria: the beginning of a protein journey
  7. Evolution of mitochondrial protein import – lessons from trypanosomes
  8. Protein import: crossing the outer membrane
  9. Biogenesis pathways of α-helical mitochondrial outer membrane proteins
  10. The structure of the TOM core complex in the mitochondrial outer membrane
  11. Porins as helpers in mitochondrial protein translocation
  12. Protein translocation beyond the outer membrane
  13. From TOM to the TIM23 complex – handing over of a precursor
  14. How to get to the other side of the mitochondrial inner membrane – the protein import motor
  15. The biogenesis of mitochondrial intermembrane space proteins
  16. Protein import by the mitochondrial disulfide relay in higher eukaryotes
  17. Mitochondrial ultrastructure and dynamics
  18. The MICOS complex, a structural element of mitochondria with versatile functions
  19. Asymmetric inheritance of mitochondria in yeast
  20. Lipid transport and mitochondrial contact sites
  21. New horizons in mitochondrial contact site research
  22. The endoplasmic reticulum-mitochondria encounter structure: coordinating lipid metabolism across membranes
  23. Lipid homeostasis in mitochondria
  24. The biogenesis of enzymes
  25. Modular assembly of yeast mitochondrial ATP synthase and cytochrome oxidase
  26. From the discovery to molecular understanding of cellular iron-sulfur protein biogenesis
  27. Mitochondrial quality control
  28. Regulation of mitochondrial plasticity by the i-AAA protease YME1L
  29. PINK1 and Parkin: team players in stress-induced mitophagy
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