Molecular movies and energy landscapes of the respiratory chain

The functionality of a cell or organelle at the molecular level is underpinned by dynamic interactions between biomolecules. These interactions may involve structural changes of the components, binding of regulatory proteins or small molecules. One system that is highly regulated by such interactions is the respiratory chain of mitochondria and aerobic bacteria. This system is composed of a number of membrane-bound enzymes that sequentially transfer electrons from low-potential donors to high-potential acceptors. The electron transfer is linked to transmembrane proton translocation, which maintains an electrochemical gradient that stores free energy.

We use time-resolved spectroscopic techniques to study the function of each component, assemblies of components as well as intact mitochondrial membranes. These mechanistic studies are combined with the use of cryogenic electron microscopy to determine structures of the respiratory enzyme components and supercomplexes. The aim is to understand function, as well as dynamics of interactions between the respiratory enzymes, at a molecular level in terms of physical mechanisms. A long-term goal is to visualize these dynamic processes in 3D to reconstruct “molecular movies” showing functional dynamics of complex molecular machines “in action” as well as the interaction choreography of these systems.