title: Distribution and dynamics of quinones in the lipid bilayer mimicking the inner membrane of mitochondria.
abstract: Quinone and its analogues (Q) constitute an important class of compounds that perform key electron transfer reactions in oxidative- and photo-phosphorylation. In the inner membrane of mitochondria, ubiquinone molecules undergo continuous redox transitions enabling electron transfer between the respiratory complexes. In such a dynamic system undergoing continuous turnover for ATP synthesis, an uninterrupted supply of substrate molecules is absolutely necessary. In the current work, we have performed atomistic molecular dynamics simulations and free energy calculations to assess the structure, dynamics, and localization of quinone and its analogues in a lipid bilayer, whose composition mimics the one in the inner mitochondrial membrane. The results show that there is a strong tendency of both quinone and quinol molecules to localize in the vicinity of the lipids' acyl groups, right under the lipid head group region. Additionally, we observe a second location in the middle of the bilayer where quinone molecules tend to stabilize. Translocation of quinone through a lipid bilayer is very fast and occurs in 10-100ns time scale, whereas the translocation of quinol is at least an order of magnitude slower. We suggest that this has important mechanistic implications given that the localization of Q ensures maximal occupancy of the Q-binding sites or Q-entry points in electron transport chain complexes, thereby maintaining an optimal turnover rate for ATP synthesis.
authors.affiliation: Department of Physics, Tampere University of Technology, P. O. Box 692, FI-33101 Tampere, Finland.
authors.forename: Petri
authors.initials: P
authors.lastname: Kaurola
authors.affiliation: Department of Physics, Tampere University of Technology, P. O. Box 692, FI-33101 Tampere, Finland; Department of Physics, University of Helsinki, P.O. Box 64, FI-00014 Helsinki, Finland.
authors.forename: Vivek
authors.initials: V
authors.lastname: Sharma
authors.affiliation: Department of Physics, Tampere University of Technology, P. O. Box 692, FI-33101 Tampere, Finland.
authors.forename: Amanda
authors.initials: A
authors.lastname: Vonk
authors.affiliation: Department of Physics, Tampere University of Technology, P. O. Box 692, FI-33101 Tampere, Finland; Department of Physics, University of Helsinki, P.O. Box 64, FI-00014 Helsinki, Finland; MEMPHYS - Center for Biomembrane Physics, University of Southern Denmark, DK-5230 Odense M, Denmark.
authors.forename: Ilpo
authors.initials: I
authors.lastname: Vattulainen
authors.affiliation: Department of Physics, Tampere University of Technology, P. O. Box 692, FI-33101 Tampere, Finland; Department of Physics, University of Helsinki, P.O. Box 64, FI-00014 Helsinki, Finland. Electronic address: tomasz.rog@helsinki.fi.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Róg
mesh_terms: D040761:Biomimetic Materials / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D008928:Mitochondria / Q000737:chemistry*; D051336:Mitochondrial Membranes / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D011809:Quinones / Q000737:chemistry*
chemical_list: D008051:Lipid Bilayers; D011809:Quinones
keywords: Biological energy transduction; Electron transport chain; Free energy calculations; Molecular dynamics simulations