Research project Function of complex I in cell respiration, photosynthesis, and mitochondrial disease
Biological energy transduction is catalyzed by membrane-bound enzymes that capture and convert chemical or light-energy to power cellular function. This project aims to elucidate how modular adaptations enable energy transducing enzymes to evolve new biological functionality.
The main focus is on the respiratory complex I-machinery that catalyzes remarkable long-range (>300 Å) coupled electron and proton transport (PCET) reactions by mechanistic principles that are unknown. We study here how modular adaptation in the core enzyme architecture allows complex I to develop functionality required for bacterial, mitochondrial, and photosynthetic energy transduction chains. To this end, we integrate methods of computational biochemistry with biochemical and biophysical experiments, as well as single particle cryo-electron microscopy (cryo-EM) studies to probe structure-function relationships on a broad range of timescales and spatial resolutions. The results are relevant for understanding mechanistic principles of energy conservation in biological membranes as well as underlying principles of human mitochondrial disease. Our studies on modular adaptions in photosynthetic variants of complex I contribute to understanding how photosynthetic organisms concentrate CO2 for the synthesis of biomass. The project is a continuation of our previously funded project by the German Research Foundation (DFG), with a new research direction developed in the current proposal.