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

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. Bru- cella-induced expression of the mitophagy receptor BNIP3L is essential for these events and relies on the iron-dependent stabili- sation 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 num- ber of reinfection events. Altogether, these findings highlight the intricate link between Brucella trafficking and the mitochondria during host cell infection.