Mitochondria vs. pathogens : the role of mitochondria in immune responses and virulence strategies targeting mitochondrial functions
Raatikainen, Ronja (2025)
2025
Bioteknologian ja biolääketieteen tekniikan kandidaattiohjelma - Bachelor's Programme in Biotechnology and Biomedical Engineering
Lääketieteen ja terveysteknologian tiedekunta - Faculty of Medicine and Health Technology
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Hyväksymispäivämäärä
2025-12-19
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:tuni-2025112610952
https://urn.fi/URN:NBN:fi:tuni-2025112610952
Tiivistelmä
Mitochondria play a central role as the primary energy producers of the cell. They are largely responsible for the cell’s metabolic functions, as well as other important processes such as signaling and cell death. Recent studies have shown that mitochondria also play a significant role in the development of the immune response and in the activation and function of immune cells. These effects on immune cell function are largely based on the modifications of mitochondrial metabolic pathways.
In addition, mitochondria can activate the immune response during cell infection through mitochondrial antiviral signaling (MAVS). MAVS proteins on the outer mitochondria membrane are activated by the presence of viral RNA and initiate the production of type I interferons. Mitochondria damaged by cell invasion release mitochondrial reactive oxygen species (mtROS) and DNA into the cytosol. The secretion of these factors has been found to influence the development of the immune response through the NLRP3 inflammasome and the cytokine production it triggers. Furthermore, mitochondrial dynamics are linked to immune response development during infections. Another important protective mechanism is mitophagy, which maintains normal mitochondrial homeostasis. Mitophagy is a form of autophagy that degrades damaged mitochondria in lysosomes. Abnormalities in mitophagy lead to increased mtROS production and apoptosis. The central role of mitochondria in cellular function makes them a prime target for invasive pathogens.
Such virulence strategies targeting mitochondria have been observed in both viruses and bacteria. RNA viruses such as SARS-Cov-2 and Hepatitis C aim to disrupt mitochondrial dynamics including fusion and fission, as part of their infection mechanism. Changes in normal mitochondrial dynamics have been linked to mtROS production and cellular oxidative stress. Alternatively, pathogens may affect mitochondrial function directly through secreted toxins. For example, the bacterium Listeria monocytogenes utilizes the Listeriolysin O (LLO) toxin to disrupt normal cellular function. Mitochondrial fragmentation caused by LLO prevents the activation of mitochondrial apoptotic signaling pathways, thereby enhancing bacterial viability, and spread. In addition, these pathogens influence mitophagy, which maintains mitochondrial homeostasis, either by inhibiting it or accelerating mitochondrial autophagy, depending on the pathogen.
In this thesis, I present the role of mitochondria in immunity and the ways in which pathogens target their virulence strategies to weaken mitochondrial function, focusing on the infection mechanisms of SARS-CoV-2 and Hepatitis C viruses, as well as the bacterium Listeria monocytogenes.
In addition, mitochondria can activate the immune response during cell infection through mitochondrial antiviral signaling (MAVS). MAVS proteins on the outer mitochondria membrane are activated by the presence of viral RNA and initiate the production of type I interferons. Mitochondria damaged by cell invasion release mitochondrial reactive oxygen species (mtROS) and DNA into the cytosol. The secretion of these factors has been found to influence the development of the immune response through the NLRP3 inflammasome and the cytokine production it triggers. Furthermore, mitochondrial dynamics are linked to immune response development during infections. Another important protective mechanism is mitophagy, which maintains normal mitochondrial homeostasis. Mitophagy is a form of autophagy that degrades damaged mitochondria in lysosomes. Abnormalities in mitophagy lead to increased mtROS production and apoptosis. The central role of mitochondria in cellular function makes them a prime target for invasive pathogens.
Such virulence strategies targeting mitochondria have been observed in both viruses and bacteria. RNA viruses such as SARS-Cov-2 and Hepatitis C aim to disrupt mitochondrial dynamics including fusion and fission, as part of their infection mechanism. Changes in normal mitochondrial dynamics have been linked to mtROS production and cellular oxidative stress. Alternatively, pathogens may affect mitochondrial function directly through secreted toxins. For example, the bacterium Listeria monocytogenes utilizes the Listeriolysin O (LLO) toxin to disrupt normal cellular function. Mitochondrial fragmentation caused by LLO prevents the activation of mitochondrial apoptotic signaling pathways, thereby enhancing bacterial viability, and spread. In addition, these pathogens influence mitophagy, which maintains mitochondrial homeostasis, either by inhibiting it or accelerating mitochondrial autophagy, depending on the pathogen.
In this thesis, I present the role of mitochondria in immunity and the ways in which pathogens target their virulence strategies to weaken mitochondrial function, focusing on the infection mechanisms of SARS-CoV-2 and Hepatitis C viruses, as well as the bacterium Listeria monocytogenes.