Project
Nicotinamide Nucleotide Transhydrogenase (NNT)
Too high concentrations of reactive oxygen species (ROS) have been linked to aging and age-related diseases. Cells have multiple mechanisms to remove these ROS, of which most use NADPH. Therefore, producing enough NADPH is important for (cellular) health. One of the producers of NADPH is the protein nicotinamide nucleotide transhydrogenase (NNT). In this project, we will research the role of NNT in relation to ROS balance.
Background
We are living in a society that has an increasing average age. With this, our society is facing more and more age-related health problems, such as neurodegenerative diseases like Alzheimer’s disease. Previous research has implicated a role for reactive oxygen species (ROS) in these age-related health problems. Although ROS are important for cellular functioning, a long-term disbalance of the production of ROS and the break down of ROS might be the difference between health and disease.
Description
In this project, we want to research the protein nicotinamide nucleotide transhydrogenase (NNT). As NNT is one of the key enzymes to produce NADPH, NNT might play a pivotal role in the removal of ROS in our cells. Therefore, the (long-term) ROS homeostasis – the balance between the production and break down of ROS – is suggested to be dependent on NNT functioning.
Interestingly, the reaction in which NNT produces NADPH is coupled to the energy production of the mitochondria. This makes NNT a unique protein. To examine this feature and its link to healthy functioning cells, we will research the activity of NNT in multiple energy states of the cells, to be able to conclude under which conditions NNT is most active. For start, we will do in vitro research using different cellular energy substrates in cells with and without a functional NNT protein. Later, we will use our in-house NNT-/- mouse model to research NNT functioning in vivo.