1. Biochemistry and Chemical Biology
  2. Cell Biology
Download icon

Tim29 is a novel subunit of the human TIM22 translocase and is involved in complex assembly and stability

  1. Yilin Kang
  2. Michael James Baker
  3. Michael Liem
  4. Jade Louber
  5. Matthew McKenzie
  6. Ishara Atukorala
  7. Ching-Seng Ang
  8. Shivakumar Keerthikumar
  9. Suresh Mathivanan
  10. Diana Stojanovski  Is a corresponding author
  1. The University of Melbourne, Australia
  2. La Trobe University, Australia
  3. Hudson Institute of Medical Research, Australia
Research Article
  • Cited 45
  • Views 2,196
  • Annotations
Cite this article as: eLife 2016;5:e17463 doi: 10.7554/eLife.17463

Abstract

The TIM22 complex mediates the import of hydrophobic carrier proteins into the mitochondrial inner membrane. While the TIM22 machinery has been well characterised in yeast, the human complex remains poorly characterised. Here, we identify Tim29 (C19orf52) as a novel, metazoan-specific subunit of the human TIM22 complex. The protein is integrated into the mitochondrial inner membrane with it's C-terminus exposed to the intermembrane space. Tim29 is required for the stability of the TIM22 complex and functions in the assembly of the hTim22. Furthermore, Tim29 contacts the Translocase of the Outer Mitochondrial Membrane, TOM complex, enabling a mechanism for transport of hydrophobic carrier substrates across the aqueous intermembrane space. Identification of Tim29 highlights the significance of analysing mitochondrial import systems across phylogenetic boundaries, which can reveal novel components and mechanisms in higher organisms.

Article and author information

Author details

  1. Yilin Kang

    Department of Biochemistry and Molecular Biology, The University of Melbourne, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  2. Michael James Baker

    Department of Biochemistry and Molecular Biology, The University of Melbourne, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  3. Michael Liem

    Department of Biochemistry and Genetics, La Trobe University, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  4. Jade Louber

    Department of Biochemistry and Molecular Biology, The University of Melbourne, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  5. Matthew McKenzie

    Centre for Genetic Diseases, Hudson Institute of Medical Research, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  6. Ishara Atukorala

    Department of Biochemistry and Genetics, La Trobe University, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  7. Ching-Seng Ang

    The Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  8. Shivakumar Keerthikumar

    Department of Biochemistry and Genetics, La Trobe University, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  9. Suresh Mathivanan

    Department of Biochemistry and Genetics, La Trobe University, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  10. Diana Stojanovski

    Department of Biochemistry and Molecular Biology, The University of Melbourne, Melbourne, Australia
    For correspondence
    d.stojanovski@unimelb.edu.au
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0199-3222

Funding

The authors declare that there was no funding for this work

Reviewing Editor

  1. Nikolaus Pfanner, University of Freiburg, Germany

Publication history

  1. Received: May 4, 2016
  2. Accepted: August 14, 2016
  3. Accepted Manuscript published: August 24, 2016 (version 1)
  4. Version of Record published: September 8, 2016 (version 2)
  5. Version of Record updated: December 1, 2016 (version 3)

Copyright

© 2016, Kang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 2,196
    Page views
  • 499
    Downloads
  • 45
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Biochemistry and Chemical Biology
    Maria Carmela Filomena et al.
    Research Article

    Myopalladin (MYPN) is a striated muscle-specific immunoglobulin domain-containing protein located in the sarcomeric Z-line and I-band. MYPN gene mutations are causative for dilated (DCM), hypertrophic and restrictive cardiomyopathy. In a yeast two-hybrid screening, MYPN was found to bind to titin in the Z-line, which was confirmed by microscale thermophoresis. Cardiac analyses of MYPN knockout (MKO) mice showed the development of mild cardiac dilation and systolic dysfunction, associated with decreased myofibrillar isometric tension generation and increased resting tension at longer sarcomere lengths. MKO mice exhibited a normal hypertrophic response to transaortic constriction (TAC), but rapidly developed severe cardiac dilation and systolic dysfunction, associated with fibrosis, increased fetal gene expression, higher intercalated disc fold amplitude, decreased calsequestrin-2 protein levels, and increased desmoplakin and SORBS2 protein levels. Cardiomyocyte analyses showed delayed Ca2+ release and reuptake in unstressed MKO mice as well as reduced Ca2+ spark amplitude post-TAC, suggesting that altered Ca2+ handling may contribute to the development of DCM in MKO mice.

    1. Biochemistry and Chemical Biology
    Xavier Portillo et al.
    Research Article Updated

    An RNA polymerase ribozyme that has been the subject of extensive directed evolution efforts has attained the ability to synthesize complex functional RNAs, including a full-length copy of its own evolutionary ancestor. During the course of evolution, the catalytic core of the ribozyme has undergone a major structural rearrangement, resulting in a novel tertiary structural element that lies in close proximity to the active site. Through a combination of site-directed mutagenesis, structural probing, and deep sequencing analysis, the trajectory of evolution was seen to involve the progressive stabilization of the new structure, which provides the basis for improved catalytic activity of the ribozyme. Multiple paths to the new structure were explored by the evolving population, converging upon a common solution. Tertiary structural remodeling of RNA is known to occur in nature, as evidenced by the phylogenetic analysis of extant organisms, but this type of structural innovation had not previously been observed in an experimental setting. Despite prior speculation that the catalytic core of the ribozyme had become trapped in a narrow local fitness optimum, the evolving population has broken through to a new fitness locale, raising the possibility that further improvement of polymerase activity may be achievable.