Renard, H.-F. | bioRxiv Science

bioRxiv2022

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 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.

microbiology↗

bioRxiv2022

Plasma membrane nanodeformations promote actin polymerisation through CIP4/CDC42 recruitment and regulate type II IFN signaling

In their environment, cells have to cope with mechanical stresses constantly. Among those, nanoscale deformations of plasma membrane induced by substrate nanotopography are now largely accepted as a biophysical stimulus influencing cell behaviour and function. However, the mechanotransduction cascades involved and their precise molecular effects on cellular physiology are still poorly understood. Here, using homemade fluorescent nanostructured cell culture surfaces, we explored the role of Bin/Amphiphysin/Rvs (BAR) domain proteins as mechanosensors of plasma membrane geometry. Our data reveal that distinct subsets of BAR proteins bind to plasma membrane deformations in a membrane curvature radius-dependent manner. Furthermore, we show that membrane curvature promotes the formation of dynamic actin structures mediated by the Rho GTPase CDC42, the F-BAR protein CIP4 and the presence of PI(4,5)P2, independently of clathrin. In addition, these actin-enriched nanodomains can serve as platforms to regulate receptor signaling as they appear to contain Interferon {gamma} receptor (IFN{gamma}-R) and to lead to the partial inhibition of IFN{gamma}-induced Janus-activated tyrosine kinase/signal transducer and activator of transcription (JAK/STAT) signaling.

cell biology↗