Researchers from the University of São Paulo (USP) in Brazil, in collaboration with colleagues from Australia, have made a significant discovery that could have implications for treating various diseases related to mitochondrial dysfunction, including cancer and autoimmune disorders. The study, published in the journal PNAS, focuses on a novel bacterial protein, mitochondrial coxiella effector F (MceF), released by the bacterium Coxiella burnetii.
C. burnetii is responsible for Q fever, a serious infection that affects both humans and animals. The bacterium employs various strategies to prevent the death of invaded cells, allowing it to multiply efficiently. One such strategy involves the modulation of glutathione peroxidase 4 (GPX4), an antioxidant enzyme located in the mitochondria, by the newly identified protein MceF.
The researchers, led by Dario Zamboni, a professor at the Ribeirão Preto Medical School, analyzed more than 130 proteins released by C. burnetii during its invasion of host cells. MceF was found to interact with GPX4, promoting an antioxidizing effect that enhances mitochondrial function. This interaction helps prevent cell damage and death, particularly when pathogens replicate inside mammalian cells.
Zamboni highlighted the bacterium’s ability to subvert cell functions, describing it as a “brilliant cell biologist” due to its efficiency in modulating host cells. Unlike other bacteria that cause disease only in large numbers, even a single C. burnetii can make a healthy person sick. The bacterium is adept at invading and controlling macrophages and monocytes, key components of the immune system.
The study not only provides insights into the strategies employed by C. burnetii but also offers valuable information on cellular functions, programmed cell death, and ways to address mitochondrial dysfunction. The researchers conducted in vitro assays and experiments involving Greater wax moth larvae to understand the bacterium’s impact on macrophages and its direct interaction with mitochondria.
Moving forward, the research will continue on two fronts. One aspect aims to deepen the understanding of other proteins of interest, while the other involves biochemical studies to elucidate further how MceF influences GPX4. Zamboni emphasized the significance of the research, noting that studying this bacterium provides a wealth of knowledge about cell signaling and death, offering novel approaches to reversing mitochondrial dysfunction without the need for new techniques.
Source: FAPESP