Host cell egress of Brucella abortus requires BNIP3L-mediated mitophagy

Jérémy Verbeke; Youri Fayt; Lisa Martin; Oya Yilmaz; Jaroslaw Sedzicki; Angéline Reboul; Michel Jadot; Patricia Renard; Christoph Dehio; Henri François Renard; Jean-Jacques Letesson; Xavier De Bolle; Thierry Arnould

doi:10.15252/embj.2022112817

Host cell egress of Brucella abortus requires BNIP3L-mediated mitophagy

Jérémy Verbeke, Youri Fayt, Lisa Martin, Oya Yilmaz, Jaroslaw Sedzicki, Angéline Reboul, Michel Jadot, Patricia Renard, Christoph Dehio, Henri François Renard, Jean-Jacques Letesson, Xavier De Bolle, Thierry Arnould

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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 intracellular bacteria and the host cell mitochondria. Here, we showed that B. abortus triggers substantive mitochondrial network fragmentation, accompanied by mitophagy and the formation of mitochondrial Brucella-containing vacuoles during the late steps of cellular infection. Brucella-induced expression of the mitophagy receptor BNIP3L is essential for these events and relies on the iron-dependent stabilisation of the hypoxia-inducible factor 1α. Functionally, BNIP3L-mediated mitophagy appears to be advantageous for bacterial exit from the host cell as BNIP3L depletion drastically reduces the number of reinfection events. Altogether, these findings highlight the intricate link between Brucella trafficking and the mitochondria during host cell infection.

Original language	English
Article number	e112817
Journal	The EMBO journal
Volume	42
Issue number	14
Early online date	25 May 2023
DOIs	https://doi.org/10.15252/embj.2022112817
Publication status	Published - 17 Jul 2023

Funding

The authors would like to thank Prof. Suzana Salcedo (University of Lyon, France) for her helpful discussions and for the generous gift of iBMDM, as well as Prof. Carles Canto (Ecole Polytechnique F\u00E9d\u00E9rale de Lausanne, Switzerland) for his helpful discussions. The authors also thank the \u201CMorphology and Imaging\u201D (Morph-Im) technological platform (University of Namur) and especially Catherine Demazy and No\u00EBlle Ninane for the advice and trainings for the initial use of the Leica TCS SP5 II confocal microscope. We also thank Dr. David Pla-Mart\u00EDn for generously providing the FIS1-GFP-mCherry reporter construct. J\u00E9r\u00E9my Verbeke is a Research Fellow (2018-2022) of the F.R.S-FNRS (Fonds de la Recherche Scientifique, Belgium). This work was also supported by two \u201CCr\u00E9dit de Recherche\u201D grants (CDR 2019-2021: \u201CMITOCHOBRU\u201D grant J.0003.20-AID 35252856 and CDR 2022-2023: \u201CBrucella and BNIP3L-mediated mitophagy\u201D grant J.0003.22 AID 40007965) obtained from the F.R.S-FNRS, as well as by a Start-Up grant obtained from the Fondation Francqui (to Henri-Fran\u00E7ois Renard) and the grant 310030B_201273 obtained from the Swiss National Science Foundation (to Christoph Dehio). The authors would like to thank Prof. Suzana Salcedo (University of Lyon, France) for her helpful discussions and for the generous gift of iBMDM, as well as Prof. Carles Canto (Ecole Polytechnique F\u00E9d\u00E9rale de Lausanne, Switzerland) for his helpful discussions. The authors also thank the \u201CMorphology and Imaging\u201D (Morph\u2010Im) technological platform (University of Namur) and especially Catherine Demazy and No\u00EBlle Ninane for the advice and trainings for the initial use of the Leica TCS SP5 II confocal microscope. We also thank Dr. David Pla\u2010Mart\u00EDn for generously providing the FIS1\u2010GFP\u2010mCherry reporter construct. J\u00E9r\u00E9my Verbeke is a Research Fellow (2018\u20102022) of the F.R.S\u2010FNRS (Fonds de la Recherche Scientifique, Belgium). This work was also supported by two \u201CCr\u00E9dit de Recherche\u201D grants (CDR 2019\u20102021: \u201CMITOCHOBRU\u201D grant J.0003.20\u2010AID 35252856 and CDR 2022\u20102023: \u201CBrucella and BNIP3L\u2010mediated mitophagy\u201D grant J.0003.22 AID 40007965) obtained from the F.R.S\u2010FNRS, as well as by a Start\u2010Up grant obtained from the Fondation Francqui (to Henri\u2010Fran\u00E7ois Renard) and the grant 310030B_201273 obtained from the Swiss National Science Foundation (to Christoph Dehio).

Funders	Funder number
Université de Lyon
École Polytechnique Fédérale de Lausanne
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung	201273
Fonds De La Recherche Scientifique - FNRS	J.0003.22 AID 40007965, J.0003.20‐AID 35252856
University of Namur	2018-2022
Fondation Francqui - Stichting	310030B_201273

Keywords

BNIP3L
Brucella
intracellular trafficking
iron
mitophagy

Access to Document

10.15252/embj.2022112817

Verbeke 2023 - EMBO J

Cite this

@article{61ac8999632847ed80fc0dee733a863e,

title = "Host cell egress of Brucella abortus requires BNIP3L-mediated mitophagy",

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 intracellular bacteria and the host cell mitochondria. Here, we showed that B. abortus triggers substantive mitochondrial network fragmentation, accompanied by mitophagy and the formation of mitochondrial Brucella-containing vacuoles during the late steps of cellular infection. Brucella-induced expression of the mitophagy receptor BNIP3L is essential for these events and relies on the iron-dependent stabilisation of the hypoxia-inducible factor 1α. Functionally, BNIP3L-mediated mitophagy appears to be advantageous for bacterial exit from the host cell as BNIP3L depletion drastically reduces the number of reinfection events. Altogether, these findings highlight the intricate link between Brucella trafficking and the mitochondria during host cell infection.",

keywords = "BNIP3L, Brucella, intracellular trafficking, iron, mitophagy",

author = "J{\'e}r{\'e}my Verbeke and Youri Fayt and Lisa Martin and Oya Yilmaz and Jaroslaw Sedzicki and Ang{\'e}line Reboul and Michel Jadot and Patricia Renard and Christoph Dehio and Renard, \{Henri Fran{\c c}ois\} and Jean-Jacques Letesson and \{De Bolle\}, Xavier and Thierry Arnould",

note = "Funding Information: The authors would like to thank Prof. Suzana Salcedo (University of Lyon, France) for her helpful discussions and for the generous gift of iBMDM, as well as Prof. Carles Canto (Ecole Polytechnique F{\'e}d{\'e}rale de Lausanne, Switzerland) for his helpful discussions. The authors also thank the “Morphology and Imaging” (Morph‐Im) technological platform (University of Namur) and especially Catherine Demazy and No{\"e}lle Ninane for the advice and trainings for the initial use of the Leica TCS SP5 II confocal microscope. We also thank Dr. David Pla‐Mart{\'i}n for generously providing the FIS1‐GFP‐mCherry reporter construct. J{\'e}r{\'e}my Verbeke is a Research Fellow (2018‐2022) of the F.R.S‐FNRS (Fonds de la Recherche Scientifique, Belgium). This work was also supported by two “Cr{\'e}dit de Recherche” grants (CDR 2019‐2021: “MITOCHOBRU” grant J.0003.20‐AID 35252856 and CDR 2022‐2023: “Brucella and BNIP3L‐mediated mitophagy” grant J.0003.22 AID 40007965) obtained from the F.R.S‐FNRS, as well as by a Start‐Up grant obtained from the Fondation Francqui (to Henri‐Fran{\c c}ois Renard) and the grant 310030B\_201273 obtained from the Swiss National Science Foundation (to Christoph Dehio). Funding Information: The authors would like to thank Prof. Suzana Salcedo (University of Lyon, France) for her helpful discussions and for the generous gift of iBMDM, as well as Prof. Carles Canto (Ecole Polytechnique F{\'e}d{\'e}rale de Lausanne, Switzerland) for his helpful discussions. The authors also thank the “Morphology and Imaging” (Morph-Im) technological platform (University of Namur) and especially Catherine Demazy and No{\"e}lle Ninane for the advice and trainings for the initial use of the Leica TCS SP5 II confocal microscope. We also thank Dr. David Pla-Mart{\'i}n for generously providing the FIS1-GFP-mCherry reporter construct. J{\'e}r{\'e}my Verbeke is a Research Fellow (2018-2022) of the F.R.S-FNRS (Fonds de la Recherche Scientifique, Belgium). This work was also supported by two “Cr{\'e}dit de Recherche” grants (CDR 2019-2021: “MITOCHOBRU” grant J.0003.20-AID 35252856 and CDR 2022-2023: “Brucella and BNIP3L-mediated mitophagy” grant J.0003.22 AID 40007965) obtained from the F.R.S-FNRS, as well as by a Start-Up grant obtained from the Fondation Francqui (to Henri-Fran{\c c}ois Renard) and the grant 310030B\_201273 obtained from the Swiss National Science Foundation (to Christoph Dehio). Publisher Copyright: {\textcopyright} 2023 The Authors.",

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doi = "10.15252/embj.2022112817",

language = "English",

volume = "42",

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T1 - Host cell egress of Brucella abortus requires BNIP3L-mediated mitophagy

AU - Verbeke, Jérémy

AU - Fayt, Youri

AU - Martin, Lisa

AU - Yilmaz, Oya

AU - Sedzicki, Jaroslaw

AU - Reboul, Angéline

AU - Jadot, Michel

AU - Renard, Patricia

AU - Dehio, Christoph

AU - Renard, Henri François

AU - Letesson, Jean-Jacques

AU - De Bolle, Xavier

AU - Arnould, Thierry

N1 - Funding Information: The authors would like to thank Prof. Suzana Salcedo (University of Lyon, France) for her helpful discussions and for the generous gift of iBMDM, as well as Prof. Carles Canto (Ecole Polytechnique Fédérale de Lausanne, Switzerland) for his helpful discussions. The authors also thank the “Morphology and Imaging” (Morph‐Im) technological platform (University of Namur) and especially Catherine Demazy and Noëlle Ninane for the advice and trainings for the initial use of the Leica TCS SP5 II confocal microscope. We also thank Dr. David Pla‐Martín for generously providing the FIS1‐GFP‐mCherry reporter construct. Jérémy Verbeke is a Research Fellow (2018‐2022) of the F.R.S‐FNRS (Fonds de la Recherche Scientifique, Belgium). This work was also supported by two “Crédit de Recherche” grants (CDR 2019‐2021: “MITOCHOBRU” grant J.0003.20‐AID 35252856 and CDR 2022‐2023: “Brucella and BNIP3L‐mediated mitophagy” grant J.0003.22 AID 40007965) obtained from the F.R.S‐FNRS, as well as by a Start‐Up grant obtained from the Fondation Francqui (to Henri‐François Renard) and the grant 310030B_201273 obtained from the Swiss National Science Foundation (to Christoph Dehio). Funding Information: The authors would like to thank Prof. Suzana Salcedo (University of Lyon, France) for her helpful discussions and for the generous gift of iBMDM, as well as Prof. Carles Canto (Ecole Polytechnique Fédérale de Lausanne, Switzerland) for his helpful discussions. The authors also thank the “Morphology and Imaging” (Morph-Im) technological platform (University of Namur) and especially Catherine Demazy and Noëlle Ninane for the advice and trainings for the initial use of the Leica TCS SP5 II confocal microscope. We also thank Dr. David Pla-Martín for generously providing the FIS1-GFP-mCherry reporter construct. Jérémy Verbeke is a Research Fellow (2018-2022) of the F.R.S-FNRS (Fonds de la Recherche Scientifique, Belgium). This work was also supported by two “Crédit de Recherche” grants (CDR 2019-2021: “MITOCHOBRU” grant J.0003.20-AID 35252856 and CDR 2022-2023: “Brucella and BNIP3L-mediated mitophagy” grant J.0003.22 AID 40007965) obtained from the F.R.S-FNRS, as well as by a Start-Up grant obtained from the Fondation Francqui (to Henri-François Renard) and the grant 310030B_201273 obtained from the Swiss National Science Foundation (to Christoph Dehio). Publisher Copyright: © 2023 The Authors.

PY - 2023/7/17

Y1 - 2023/7/17

N2 - 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 intracellular bacteria and the host cell mitochondria. Here, we showed that B. abortus triggers substantive mitochondrial network fragmentation, accompanied by mitophagy and the formation of mitochondrial Brucella-containing vacuoles during the late steps of cellular infection. Brucella-induced expression of the mitophagy receptor BNIP3L is essential for these events and relies on the iron-dependent stabilisation of the hypoxia-inducible factor 1α. Functionally, BNIP3L-mediated mitophagy appears to be advantageous for bacterial exit from the host cell as BNIP3L depletion drastically reduces the number of reinfection events. Altogether, these findings highlight the intricate link between Brucella trafficking and the mitochondria during host cell infection.

AB - 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 intracellular bacteria and the host cell mitochondria. Here, we showed that B. abortus triggers substantive mitochondrial network fragmentation, accompanied by mitophagy and the formation of mitochondrial Brucella-containing vacuoles during the late steps of cellular infection. Brucella-induced expression of the mitophagy receptor BNIP3L is essential for these events and relies on the iron-dependent stabilisation of the hypoxia-inducible factor 1α. Functionally, BNIP3L-mediated mitophagy appears to be advantageous for bacterial exit from the host cell as BNIP3L depletion drastically reduces the number of reinfection events. Altogether, these findings highlight the intricate link between Brucella trafficking and the mitochondria during host cell infection.

KW - BNIP3L

KW - Brucella

KW - intracellular trafficking

KW - iron

KW - mitophagy

UR - https://www.scopus.com/pages/publications/85159950459

U2 - 10.15252/embj.2022112817

DO - 10.15252/embj.2022112817

M3 - Article

C2 - 37232029

SN - 0261-4189

VL - 42

JO - The EMBO journal

JF - The EMBO journal

IS - 14

M1 - e112817

ER -

Host cell egress of Brucella abortus requires BNIP3L-mediated mitophagy

Abstract

Funding

Keywords

Access to Document

Other files and links

Fingerprint

To eat or not to eat mitochondria? How do host cells cope with mitophagy upon bacterial infection?

Biological Security Laboratory Level 3 (BL3)

Morphology - Imaging

Cite this

Host cell egress of Brucella abortus requires BNIP3L-mediated mitophagy

Abstract

Funding

Keywords

Access to Document

Other files and links

Fingerprint

Research output

To eat or not to eat mitochondria? How do host cells cope with mitophagy upon bacterial infection?

Equipment

Biological Security Laboratory Level 3 (BL3)

Morphology - Imaging

Cite this