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Unveiling Xenobiotic Transport and Effects in Isolated Mitochondria: Insights from Respirometric and Enzymatic Assays
Published on: March 7, 2025
Mitochondria: a target for bacteria
Elodie Lobet1, Jean-Jacques Letesson2, Thierry Arnould1
1Laboratory of Biochemistry and Cellular Biology (URBC), NAmur Research Institute for LIfe Science (NARILIS), University of Namur, 61 Rue de Bruxelles, 5000 Namur, Belgium.
Abstract:
Eukaryotic cells developed strategies to detect and eradicate infections. The innate immune system, which is the first line of defence against invading pathogens, relies on the recognition of molecular patterns conserved among pathogens. Pathogen associated molecular pattern binding to pattern recognition receptor triggers the activation of several signalling pathways leading to the establishment of a pro-inflammatory state required to control the infection. In addition, pathogens evolved to subvert those responses (with passive and active strategies) allowing their entry and persistence in the host cells and tissues. Indeed, several bacteria actively manipulate immune system or interfere with the cell fate for their own benefit. One can imagine that bacterial effectors can potentially manipulate every single organelle in the cell. However, the multiple functions fulfilled by mitochondria especially their involvement in the regulation of innate immune response, make mitochondria a target of choice for bacterial pathogens as they are not only a key component of the central metabolism through ATP production and synthesis of various biomolecules but they also take part to cell signalling through ROS production and control of calcium homeostasis as well as the control of cell survival/programmed cell death. Furthermore, considering that mitochondria derived from an ancestral bacterial endosymbiosis, it is not surprising that a special connection does exist between this organelle and bacteria. In this review, we will discuss different mitochondrial functions that are affected during bacterial infection as well as different strategies developed by bacterial pathogens to subvert functions related to calcium homeostasis, maintenance of redox status and mitochondrial morphology.
Insights
Bacteria target mitochondria, crucial for innate immunity and cell signaling, to establish infections. This review details how pathogens manipulate mitochondrial functions like calcium balance and redox status for survival.
Area of Science:
- Cell Biology
- Immunology
- Microbiology
Background:
- Eukaryotic cells possess innate immune systems to detect and eliminate pathogens through pattern recognition receptors.
- Pathogens have evolved mechanisms to evade or subvert these immune responses, enabling host cell invasion and persistence.
- Mitochondria play critical roles in cellular metabolism, signaling (ROS, calcium), and cell death, making them key targets for bacterial manipulation.
Purpose of the Study:
- To review the diverse functions of mitochondria that are impacted during bacterial infections.
- To explore the strategies employed by bacterial pathogens to subvert mitochondrial functions.
- To highlight the intricate relationship between bacteria and mitochondria in the context of host-pathogen interactions.
Main Methods:
- Literature review focusing on bacterial manipulation of mitochondrial functions.
- Analysis of pathogen strategies targeting calcium homeostasis, redox status, and mitochondrial morphology.
- Synthesis of current knowledge on host-pathogen interactions at the mitochondrial level.
Main Results:
- Bacterial pathogens actively target mitochondria to disrupt host defenses and promote their survival.
- Specific bacterial effectors interfere with mitochondrial calcium uptake and release, altering signaling pathways.
- Pathogens manipulate mitochondrial redox balance and morphology to evade immune detection and facilitate replication.
Conclusions:
- Mitochondria are central players in the innate immune response and are frequently targeted by bacterial pathogens.
- Understanding how bacteria subvert mitochondrial functions provides insights into infection pathogenesis.
- Targeting mitochondrial pathways could offer novel therapeutic strategies against bacterial infections.
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