When mitophagy dictates the outcome of cellular infection: the case of Brucella abortus

ABSTRACT

Mitochondria are at the basis of various cellular functions ranging from metabolism and redox homeostasis to inflammation and cell death regulation. Mitochondria therefore constitute an attractive target for invading pathogens to fulfil their infectious cycle. This involves the modulation to their advantage of mitochondrial metabolism and dynamics, including the controlled degradation of mitochondria through mitophagy. Mitophagy might for instance be beneficial for bacterial survival as it can clear bactericidal mitochondrial ROS produced by damaged organelle fragments from the intracellular niche. In the case of the bacterial pathogen Brucella abortus, mitophagy induction has another role in the intracellular lifecycle of the bacteria. Indeed, in our study, we showed that B. abortus triggers an iron-dependent BNIP3L-mediated mitophagy response required for proper bacterial egress and infection of neighboring cells. These results highlight the diversity of mitophagy processes that might be crucial for several stages of cellular infection.

KEYWORDS:

• BNIP3L
• Brucella
• HIF1A
• intracellular trafficking
• iron
• mitophagy

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

Jérémy Verbeke was a Research Fellow (2018-2022) of the F.R.S-FNRS (Fonds de la Recherche Scientifique, Belgium). Current address of Jérémy Verbeke, Inflammation Research Center (IRC), UGent: [email protected]. 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.