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My research plan aims at understanding the role and function of hPNPase in the intermembrane space of the mitochondria. My working hypothesis is that hPNPase displays two modes of action on its RNA substrates, and the protective one could be exploited functionally in the IMS, where the enzyme would be RNA-mediated regulator of mitochondria function. On the other hand, in the mitochondrial matrix hPNPase in complex with Suv3 would always act in a degradative mode (Figure 1). This way, by physical separation of hPNPase in two different compartments, both its activities could be supporting optimal performance of the mitochondria.
I would like to conduct biochemical and molecular biology experiments that will determine if hPNPase can function as an RNA regulatory factor as well as an RNA degrading enzyme. I also plan to determine the precise three-dimensional structure of hPNPase using cryo-electron microscopy, a rapidly evolving technique allowing scientists all over the world to gain insight into different complicated macromolecular assemblies. My planned research will help us understand the role of human PNPase in the mitochondrial intermembrane space, and with such knowledge we could be one step closer to recognise causes of some mitochondrial disorders.