Galemou Yoga 2019 Biochim Biophys Acta Bioenerg

Galemou Yoga E, Haapanen O, Wittig I, Siegmund K, Sharma V, Zickermann V (2019) Mutations in a conserved loop in the PSST subunit of respiratory complex I affect ubiquinone binding and dynamics. https://doi.org/10.1016/j.bbabio.2019.06.006

» Biochim Biophys Acta Bioenerg 1860:573-81. PMID: 31226318 Open Access

Galemou Yoga Etienne, Haapanen Outi, Wittig Ilka, Siegmund Karin, Sharma Vivek, Zickermann Volker (2019) Biochim Biophys Acta Bioenerg

Abstract: Respiratory complex I catalyses the reduction of ubiquinone (Q) from NADH coupled to proton pumping across the inner membrane of mitochondria. The electrical charging of the inner mitochondrial membrane drives the synthesis of ATP, which is used to power biochemical reactions of the cell. The recent surge in structural data on complex I from bacteria and mitochondria have contributed to significant understanding of its molecular architecture. However, despite these accomplishments, the role of various subdomains in redox-coupled proton pumping remains entirely unclear. In this work, we have mutated conserved residues in the loop of the PSST subunit that faces the ~30 Å long unique Q-binding tunnel of respiratory complex I. The data show a drastic decrease in Q reductase activity upon mutating several residues despite full assembly of the complex. In-silico modeling and multiple microsecond long molecular dynamics simulations of wild-type and enzyme variants with exchanges of conserved arginine residues revealed remarkable ejection of the bound Q from the site near terminal electron donor N2. Based on experiments and long-time scale molecular simulations, we identify microscopic elements that dynamically control the diffusion of Q and are central to redox-coupled proton pumping in respiratory complex I. • Keywords: Cell respiration, Electron transfer, Proton pumping, Quinone dynamics, Redox-coupled proton pumping • Bioblast editor: Plangger M

Labels: MiParea: mt-Structure;fission;fusion 

Enzyme: Complex I