By virtue of their semi-autonomous ability to modulate DNA and protein synthesis, metabolism, and viability, mitochondria play a central role in regulating cell performance. In immune cells, mitochondria provide the necessary energetic resources to adapt to the increasing cellular demands upon activation. This adaptation involves a series of morphological remodeling and transcriptional regulation to facilitate the production of chemo and cytokines necessary to mediate an immune response. To efficiently perform these functions, mitochondria are equipped with a specific set of transporters and ion channels to maintain the anion and cation homeostasis essential for a well-controlled biogenesis of mitochondrial metabolites. Recent research identified dysregulation of many of the components of mitochondrial machinery as significant factors underlying the development of autoimmune and chronic inflammatory diseases but the exact molecular mechanisms of pathogenesis remain to be fully elucidated.
Research in the last few decades identified ion channels located at the inner or outer mitochondrial membranes and showed the beneficial effects of targeting these channels in cancer models. Furthermore, growing evidence indicates an important role of many of these channels in regulating the function of innate immune cells but the role of these channels in T cells is less understood and thus requires further exploration. Genetic ablation or pharmacological targeting of mitochondrial ion channels results often in depolarization of mitochondrial membranes, intolerably high ROS levels, and overload with critical ions such as Ca2+ eventually triggering cell death. The current issue aims to understand how modulation of mitochondrial ion channels through different regulatory mechanisms apart from extreme intervention results in fine-tuning of T cell function and thus determines the outcome of an immune response.
Specifically, this research topic will focus on:
- Studying if and how the function of mitochondrial ion channels is altered in correlation with different cellular subsets or activation states.
- The effect of manipulation of mitochondrial ion channel function on kinetics or T cell activation or proliferation and terminal functions such as cytotoxic activity or cytokine production
- Regulatory mechanisms of mitochondrial ion channels that result in alteration of metabolic profile of T cells with implication on their immune functions.
- How interventions with mitochondrial ion channel function contribute to the pathogenesis of T cells in autoimmune or inflammatory disease development or progression.
By virtue of their semi-autonomous ability to modulate DNA and protein synthesis, metabolism, and viability, mitochondria play a central role in regulating cell performance. In immune cells, mitochondria provide the necessary energetic resources to adapt to the increasing cellular demands upon activation. This adaptation involves a series of morphological remodeling and transcriptional regulation to facilitate the production of chemo and cytokines necessary to mediate an immune response. To efficiently perform these functions, mitochondria are equipped with a specific set of transporters and ion channels to maintain the anion and cation homeostasis essential for a well-controlled biogenesis of mitochondrial metabolites. Recent research identified dysregulation of many of the components of mitochondrial machinery as significant factors underlying the development of autoimmune and chronic inflammatory diseases but the exact molecular mechanisms of pathogenesis remain to be fully elucidated.
Research in the last few decades identified ion channels located at the inner or outer mitochondrial membranes and showed the beneficial effects of targeting these channels in cancer models. Furthermore, growing evidence indicates an important role of many of these channels in regulating the function of innate immune cells but the role of these channels in T cells is less understood and thus requires further exploration. Genetic ablation or pharmacological targeting of mitochondrial ion channels results often in depolarization of mitochondrial membranes, intolerably high ROS levels, and overload with critical ions such as Ca2+ eventually triggering cell death. The current issue aims to understand how modulation of mitochondrial ion channels through different regulatory mechanisms apart from extreme intervention results in fine-tuning of T cell function and thus determines the outcome of an immune response.
Specifically, this research topic will focus on:
- Studying if and how the function of mitochondrial ion channels is altered in correlation with different cellular subsets or activation states.
- The effect of manipulation of mitochondrial ion channel function on kinetics or T cell activation or proliferation and terminal functions such as cytotoxic activity or cytokine production
- Regulatory mechanisms of mitochondrial ion channels that result in alteration of metabolic profile of T cells with implication on their immune functions.
- How interventions with mitochondrial ion channel function contribute to the pathogenesis of T cells in autoimmune or inflammatory disease development or progression.
