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BNIP3L-mediated mitophagy triggered by Brucella in host cells is required for bacterial egress

Jérémy Verbeke, Youri Fayt, Lisa Martin, Oya Yilmaz, View ORCID ProfileJaroslaw Sedzicki, Angeline Reboul, View ORCID ProfileMichel Jadot, View ORCID ProfilePatricia Renard, View ORCID ProfileChristoph Dehio, View ORCID ProfileHenri-François Renard, View ORCID ProfileJean-Jacques Letesson, View ORCID ProfileXavier De Bolle, View ORCID ProfileThierry Arnould
doi: https://doi.org/10.1101/2022.08.31.505824
Jérémy Verbeke
1Research Unit in Cell Biology (URBC) – Namur Research Institute for Life Sciences (NARILIS), University of Namur, 5000 Namur, Belgium
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Youri Fayt
1Research Unit in Cell Biology (URBC) – Namur Research Institute for Life Sciences (NARILIS), University of Namur, 5000 Namur, Belgium
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Lisa Martin
1Research Unit in Cell Biology (URBC) – Namur Research Institute for Life Sciences (NARILIS), University of Namur, 5000 Namur, Belgium
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Oya Yilmaz
1Research Unit in Cell Biology (URBC) – Namur Research Institute for Life Sciences (NARILIS), University of Namur, 5000 Namur, Belgium
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Jaroslaw Sedzicki
4Biozentrum, University of Basel, 4056 Basel, Switzerland
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  • ORCID record for Jaroslaw Sedzicki
Angeline Reboul
2Research Unit in Microorganisms Biology (URBM) – Namur Research Institute for Life Sciences (NARILIS), University of Namur, 5000 Namur, Belgium
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Michel Jadot
3Research Unit in Molecular Physiology (URPhyM) – Namur Research Institute for Life Sciences (NARILIS), University of Namur, 5000 Namur, Belgium
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Patricia Renard
1Research Unit in Cell Biology (URBC) – Namur Research Institute for Life Sciences (NARILIS), University of Namur, 5000 Namur, Belgium
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  • ORCID record for Patricia Renard
Christoph Dehio
4Biozentrum, University of Basel, 4056 Basel, Switzerland
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  • ORCID record for Christoph Dehio
Henri-François Renard
1Research Unit in Cell Biology (URBC) – Namur Research Institute for Life Sciences (NARILIS), University of Namur, 5000 Namur, Belgium
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Jean-Jacques Letesson
2Research Unit in Microorganisms Biology (URBM) – Namur Research Institute for Life Sciences (NARILIS), University of Namur, 5000 Namur, Belgium
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Xavier De Bolle
2Research Unit in Microorganisms Biology (URBM) – Namur Research Institute for Life Sciences (NARILIS), University of Namur, 5000 Namur, Belgium
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Thierry Arnould
1Research Unit in Cell Biology (URBC) – Namur Research Institute for Life Sciences (NARILIS), University of Namur, 5000 Namur, Belgium
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  • For correspondence: thierry.arnould@unamur.be
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ABSTRACT

The facultative intracellular pathogen Brucella abortus interacts with several organelles of the host cell to reach its replicative niche inside the endoplasmic reticulum. However, little is known about the interplay between the bacteria and the host cell mitochondria. Here, we showed that B. abortus triggers a strong mitochondrial network fragmentation accompanied by mitophagy and the formation of mitochondrial Brucella-containing vacuoles in the late steps of cellular infection. The expression of the mitophagy receptor BNIP3L induced by B. abortus is essential for these events and relies on the iron-dependent stabilization of the hypoxia-inducible factor 1 alpha. Functionally, BNIP3L-mediated mitophagy appears to be advantageous for bacterial exit of the host cell as BNIP3L depletion drastically reduced the number of reinfection events. Altogether, these findings highlight the intricate link between Brucella trafficking and the mitochondria during host cell infection.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵# Co-last senior authors

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted August 31, 2022.
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BNIP3L-mediated mitophagy triggered by Brucella in host cells is required for bacterial egress
Jérémy Verbeke, Youri Fayt, Lisa Martin, Oya Yilmaz, Jaroslaw Sedzicki, Angeline Reboul, Michel Jadot, Patricia Renard, Christoph Dehio, Henri-François Renard, Jean-Jacques Letesson, Xavier De Bolle, Thierry Arnould
bioRxiv 2022.08.31.505824; doi: https://doi.org/10.1101/2022.08.31.505824
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BNIP3L-mediated mitophagy triggered by Brucella in host cells is required for bacterial egress
Jérémy Verbeke, Youri Fayt, Lisa Martin, Oya Yilmaz, Jaroslaw Sedzicki, Angeline Reboul, Michel Jadot, Patricia Renard, Christoph Dehio, Henri-François Renard, Jean-Jacques Letesson, Xavier De Bolle, Thierry Arnould
bioRxiv 2022.08.31.505824; doi: https://doi.org/10.1101/2022.08.31.505824

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