Researchers at the University of São Paulo (USP) in Brazil, partnering with colleagues in Australia, have identified a novel bacterial protein that can keep human cells healthy even when the cells have a heavy bacterial burden. The discovery could lead to new treatments for a wide array of diseases relating to mitochondrial dysfunction, such as cancer and auto-immune disorders. Mitochondria are organelles that supply most of the chemical energy needed to power cells' biochemical reactions.
An article on the study is published in the journal PNAS. The researchers analyzed more than 130 proteins released by Coxiella burnetii when this bacterium invades host cells, and found at least one to be capable of prolonging cell longevity by acting directly on mitochondria.
After invading host cells, C. burnetii releases a hitherto unknown protein, which the authors call mitochondrial coxiella effector F (MceF). MceF interacts with glutathione peroxidase 4 (GPX4), an anti-oxidant enzyme located in the mitochondria, to improve mitochondrial function by promoting an anti-oxidizing effect that averts cell damage and death, which may occur when pathogens replicate inside mammalian cells.
"C. burnetii uses various strategies to prevent the death of invaded cells and multiply inside them. One is modulation of GPX4 by MceF , the mechanism we discovered and reported in this article. Reallocation of these proteins in cellular mitochondria enables mammalian cells to live longer even when they're infected with a very large bacterial burden," said Dario Zamboni, one of the corresponding authors of the article and a professor at the Ribeirão Preto Medical School (FMRP-USP).
The study was conducted at the Center for Research on Inflammatory Diseases (CRID), one of FAPESP's Research, Innovation and Dissemination Centers (RIDCs), in collaboration with Hayley Newton, a professor at Monash University in Australia. Funding was also provided by FAPESP via a project coordinated by Zamboni.
"Basically, we discovered a strategy used by C. burnetii to keep cells healthy for longer while replicating intensely. We found…
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