Tryparedoxin peroxidase-deficiency commits trypanosomes to ferroptosis-type cell death

  1. Marta Bogacz
  2. R Luise Krauth-Siegel  Is a corresponding author
  1. Universität Heidelberg, Germany

Abstract

Tryparedoxin peroxidases, distant relatives of glutathione peroxidase 4 in higher eukaryotes, are responsible for the detoxification of lipid-derived hydroperoxides in African trypanosomes. The lethal phenotype of procyclic Trypanosoma brucei that lack the enzymes fulfils all criteria defining a form of regulated cell death termed ferroptosis. Viability of the parasites is preserved by α-tocopherol, ferrostatin-1, liproxstatin-1 and deferoxamine. Without protecting agent, the cells display, primarily mitochondrial, lipid peroxidation, loss of the mitochondrial membrane potential and ATP depletion. Sensors for mitochondrial oxidants and chelatable iron as well as overexpression of a mitochondrial iron-superoxide dismutase attenuate the cell death. Electron microscopy revealed mitochondrial matrix condensation and enlarged cristae. The peroxidase-deficient parasites are subject to lethal iron-induced lipid peroxidation that probably originates at the inner mitochondrial membrane. Taken together, ferroptosis is an ancient cell death program that can occur at individual subcellular membranes and is counterbalanced by evolutionary distant thiol peroxidases.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Marta Bogacz

    Biochemie-Zentrum (BZH), Universität Heidelberg, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. R Luise Krauth-Siegel

    Biochemie-Zentrum (BZH), Universität Heidelberg, Heidelberg, Germany
    For correspondence
    luise.krauth-siegel@bzh.uni-heidelberg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2164-8116

Funding

Deutsche Forschungsgemeinschaft (Kr1241/5-1)

  • R Luise Krauth-Siegel

Deutsche Forschungsgemeinschaft (Kr1241/8-1)

  • R Luise Krauth-Siegel

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Marcus Conrad, Helmholtz Zentrum München

Publication history

  1. Received: April 12, 2018
  2. Accepted: July 24, 2018
  3. Accepted Manuscript published: July 26, 2018 (version 1)
  4. Version of Record published: August 30, 2018 (version 2)

Copyright

© 2018, Bogacz & Krauth-Siegel

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. Marta Bogacz
  2. R Luise Krauth-Siegel
(2018)
Tryparedoxin peroxidase-deficiency commits trypanosomes to ferroptosis-type cell death
eLife 7:e37503.
https://doi.org/10.7554/eLife.37503

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