DBIO Thesis Prize Winner: Jonathon L. YulyElectron bifurcation and correlations in biological energy transduction

Electron bifurcation is an energy transduction process found across the tree of life, including complex III of the electron transport chain. Electron bifurcation drives electrons thermodynamically uphill by leveraging the downhill motion of other electrons. In fact, electron bifurcation can be fully electrochemically reversible, so that energy transduction occurs with near perfect thermodynamic efficiency. Electron bifurcation is a chemically challenging process because productive electron transfers must compete with strongly driven short-circuiting events. For decades, the absence of these short-circuits was shrouded in mystery, and all attempts towards synthetic electron bifurcation failed. Recently, we predicted that a conserved free energy landscape naturally prevents these short-circuiting electron transfers by large Boltzmann weights against microstates that initiate short-circuit events. Remarkably, although Boltzmann weights qualitatively capture the impact of the landscape on the short-circuit turnover, mean field transport theories fail to capture the efficient energy transduction, and instead predict short-circuiting, implying that correlations between redox cofactors cannot be naïvely neglected. Upon further exploration, this seems general for all energy transducing systems: mean field transport theory cannot capture the efficient energy transduction observed in biology. Correlations seem necessary, but which ones?