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

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.

Infection of Endothelial Cells with Acinetobacter baumannii Reveals Remodelling of Mitochondrial Protein Complexes

“…(B) Quantification of the mitochondrial endpoint/branched point ratio (EBR) in HUVECs infected with A. baumannii AB_1372 or AB_2778 for 16 h in comparison to uninfected cells. EBR is defined as the sum of all endpoints divided by the sum of all branched points ( 32 , 33 ). Data are presented as means with 95% confidence intervals from approximately 150 cells quantified for each condition ( n = 3).…”

“…To further assess the impact on mitochondrial morphology on infected HUVECs, the length and branching of mitochondrial networks were analyzed from TOM20 immunostainings and the endpoint/branched point ratio (EBR) was calculated ( 32 , 33 ) ( Fig. 6B ).…”

“…Samples were mounted on glass slides using Fluoprep (Agilent Dako) and analyzed by fluorescence microscopy (Nikon Eclipse Ci-L). The branching status of mitochondrial network was determined by calculating the mean of endpoint/branched point ratio (EBR) of mitochondrial particles in approximately 150 cells for each condition, employing a software pipeline as previously described ( 32 , 33 , 56 ). For analysis of mitophagy, HUVECs were seeded into 96-well plates and infected with A. baumannii (MOI, 100) in ECGM.…”

Integrative analysis highlights molecular and immune responses of tick Amblyomma americanum to Escherichia coli challenge

“…According to this discovery, ticks may initiate mitophagy in response to E. coli treatment, maybe as a defense mechanism to remove damaged mitochondria and preserve cellular homeostasis. Other studies have also noted the role of mitophagy in the tick’s response to bacterial challenge, highlighting the significance of this mechanism as a conserved method of immunological modulation and cellular quality control ( Chang et al., 2022 ; Verbeke et al., 2022 ). Additionally, compared to the 6 h and 24 h treatments, the expression levels of “response to oxidative stress” genes were higher in the 3 h and 12 h treatments.…”