Peroxisomal lactate dehydrogenase is generated by translational readthrough in mammals

  1. Fabian Schueren
  2. Thomas Lingner
  3. Rosemol George
  4. Julia Hofhuis
  5. Corinna Dickel
  6. Jutta Gärtner
  7. Sven Thoms  Is a corresponding author
  1. University Medical Center, Georg-August-University Göttingen, Germany
  2. Institute for Microbiology and Genetics, Georg-August-University Göttingen, Germany

Abstract

Translational readthrough gives rise to low abundance proteins with C-terminal extensions beyond the stop codon. To identify functional translational readthrough, we estimated the readthrough propensity (RTP) of all stop codon contexts of the human genome by a new regression model in silico, identified a nucleotide consensus motif for high RTP by using this model, and analyzed all readthrough extensions in silico with a new predictor for peroxisomal targeting signal type 1 (PTS1). Lactate dehydrogenase B (LDHB) showed the highest combined RTP and PTS1 probability. Experimentally we show that at least 1.6% of the total cellular LDHB getting targeted to the peroxisome by a conserved hidden PTS1. The readthrough-extended lactate dehydrogenase subunit LDHBx can also co-import LDHA, the other LDH subunit into peroxisomes. Peroxisomal LDH is conserved in mammals and likely contributes to redox equivalent regeneration in peroxisomes.

Article and author information

Author details

  1. Fabian Schueren

    University Medical Center, Georg-August-University Göttingen, Göttingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Thomas Lingner

    Institute for Microbiology and Genetics, Georg-August-University Göttingen, Göttingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Rosemol George

    University Medical Center, Georg-August-University Göttingen, Göttingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Julia Hofhuis

    University Medical Center, Georg-August-University Göttingen, Göttingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Corinna Dickel

    University Medical Center, Georg-August-University Göttingen, Göttingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Jutta Gärtner

    University Medical Center, Georg-August-University Göttingen, Göttingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Sven Thoms

    University Medical Center, Georg-August-University Göttingen, Göttingen, Germany
    For correspondence
    sven.thoms@med.uni-goettingen.de
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Nahum Sonenberg, McGill University, Canada

Version history

  1. Received: June 9, 2014
  2. Accepted: September 22, 2014
  3. Accepted Manuscript published: September 23, 2014 (version 1)
  4. Version of Record published: October 16, 2014 (version 2)

Copyright

© 2014, Schueren 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.

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  1. Fabian Schueren
  2. Thomas Lingner
  3. Rosemol George
  4. Julia Hofhuis
  5. Corinna Dickel
  6. Jutta Gärtner
  7. Sven Thoms
(2014)
Peroxisomal lactate dehydrogenase is generated by translational readthrough in mammals
eLife 3:e03640.
https://doi.org/10.7554/eLife.03640

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https://doi.org/10.7554/eLife.03640

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