Description:   
Biological energy conversion is catalyzed by gigantic membrane-bound protein complexes that transduce redox energy into a trans-membrane proton gradient, powering the synthesis of ATP. Yet, despite significant advances, the molecular principles of these long-range proton transfer reactions remain poorly understood, and a major scientific challenge. In this talk, I describe our integrative mechanistic exploration of biological energy transduction, where we combine biophysical, computational, and structural approaches to derive a molecular understanding of these intricate processes. I describe our recent work on the highly intricate Complex I machinery, catalyzing a >200 Å redox-driven proton transfer reaction. Our findings reveal that Complex I controls long-range proton transfer reactions by intrinsic electric field effects that result in conformational and hydration changes, mediated by allosteric effects. We find that mutations of key residues mediating this process results in a perturbed coupling effect that result in development of severe mitochondrial diseases. I will also discuss our recent work on addressing the function of respiratory supercomplexes, and how the formation of such molecular assemblies affects key protein-lipid interactions. On a general level, our findings reveal novel energy transduction mechanism, with striking similarities amongst different biological systems.