Oxidation of cellular amino acid pools leads to cytotoxic mistranslation of the genetic code

  1. Tammy Bullwinkle
  2. Noah M Reynolds
  3. Medha Raina
  4. Adil B Moghal
  5. Eleftheria Matsa
  6. Andrei Rajkovic
  7. Huseyin Kayadibi
  8. Farbod Fazlollahi
  9. Christopher Ryan
  10. Nathaniel Howitz
  11. Kym F Faull
  12. Beth Lazazzera
  13. Michael Ibba  Is a corresponding author
  1. Ohio State University, United States
  2. Adana Military Hospital, Turkey
  3. Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, United States
  4. California Department of Toxic Substances Control, United States
  5. University of California, Los Angeles, United States

Abstract

Aminoacyl-tRNA synthetases use a variety of mechanisms to ensure fidelity of the genetic code and ultimately select the correct amino acids to be used in protein synthesis. The physiological necessity of these quality control mechanisms in different environments remains unclear, as the cost versus benefit of accurate protein synthesis is difficult to predict. We show that in Escherichia coli, a non-coded amino acid produced through oxidative damage is a significant threat to the accuracy of protein synthesis and must be cleared by phenylalanine-tRNA synthetase in order to prevent cellular toxicity caused by mis-synthesized proteins. These findings demonstrate how stress can lead to the accumulation of non-canonical amino acids that must be excluded from the proteome in order to maintain cellular viability.

Article and author information

Author details

  1. Tammy Bullwinkle

    Ohio State University, Columbus, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Noah M Reynolds

    Ohio State University, Columbus, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Medha Raina

    Ohio State University, Columbus, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Adil B Moghal

    Ohio State University, Columbus, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Eleftheria Matsa

    Ohio State University, Columbus, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Andrei Rajkovic

    Ohio State University, Columbus, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Huseyin Kayadibi

    Adana Military Hospital, Adana, Turkey
    Competing interests
    The authors declare that no competing interests exist.
  8. Farbod Fazlollahi

    Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Christopher Ryan

    California Department of Toxic Substances Control, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Nathaniel Howitz

    University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Kym F Faull

    Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Beth Lazazzera

    University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Michael Ibba

    Ohio State University, Columbus, United States
    For correspondence
    ibba.1@att.net
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Gisela Storz, National Institute of Child Health and Human Development, United States

Publication history

  1. Received: February 10, 2014
  2. Accepted: May 29, 2014
  3. Accepted Manuscript published: June 2, 2014 (version 1)
  4. Version of Record published: June 24, 2014 (version 2)

Copyright

© 2014, Bullwinkle 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. Tammy Bullwinkle
  2. Noah M Reynolds
  3. Medha Raina
  4. Adil B Moghal
  5. Eleftheria Matsa
  6. Andrei Rajkovic
  7. Huseyin Kayadibi
  8. Farbod Fazlollahi
  9. Christopher Ryan
  10. Nathaniel Howitz
  11. Kym F Faull
  12. Beth Lazazzera
  13. Michael Ibba
(2014)
Oxidation of cellular amino acid pools leads to cytotoxic mistranslation of the genetic code
eLife 3:e02501.
https://doi.org/10.7554/eLife.02501

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