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. image The facultative intracellular pathogen Brucella abortus forms a replicative niche in the endoplasmic reticulum and hijacks the autophagic machinery for its egress from the host cell. This study shows that B. abortus induces BNIP3L‐mediated mitophagy, which is required for bacterial egress and infection of neighbouring cells. B. abortus triggers BNIP3L‐mediated mitophagy during the late steps of cellular infection. B. abortus induces BNIP3L expression in a manner dependent on iron and HIF‐1α stabilization. Iron and BNIP3L‐mediated mitophagy are required for bacterial egress from host cells. B. abortus are found inside mitochondria of HeLa cells and immortalized bone marrow‐derived macrophages.