title: From protons to OXPHOS supercomplexes and Alzheimer's disease: structure-dynamics-function relationships of energy-transducing membranes.
abstract: By the elucidation of high-resolution structures the view of the bioenergetic processes has become more precise. But in the face of these fundamental advances, many problems are still unresolved. We have examined a variety of aspects of energy-transducing membranes from large protein complexes down to the level of protons and functional relevant picosecond protein dynamics. Based on the central role of the ATP synthase for supplying the biological fuel ATP, one main emphasis was put on this protein complex from both chloroplast and mitochondria. In particular the stoichiometry of protons required for the synthesis of one ATP molecule and the supramolecular organisation of ATP synthases were examined. Since formation of supercomplexes also concerns other complexes of the respiratory chain, our work was directed to unravel this kind of organisation, e.g. of the OXPHOS supercomplex I(1)III(2)IV(1), in terms of structure and function. Not only the large protein complexes or supercomplexes work as key players for biological energy conversion, but also small components as quinones which facilitate the transfer of electrons and protons. Therefore, their location in the membrane profile was determined by neutron diffraction. Physico-chemical features of the path of protons from the generators of the electrochemical gradient to the ATP synthase, as well as of their interaction with the membrane surface, could be elucidated by time-resolved absorption spectroscopy in combination with optical pH indicators. Diseases such as Alzheimer's dementia (AD) are triggered by perturbation of membranes and bioenergetics as demonstrated by our neutron scattering studies.
authors.affiliation: Department of Chemistry, Technische Universität Darmstadt, Petersenstrasse 22, D-64287 Darmstadt, Germany. seelert@hrzpub.tu-darmstadt.de
authors.forename: H
authors.initials: H
authors.lastname: Seelert
authors.forename: D N
authors.initials: DN
authors.lastname: Dani
authors.forename: S
authors.initials: S
authors.lastname: Dante
authors.forename: T
authors.initials: T
authors.lastname: Hauss
authors.forename: F
authors.initials: F
authors.lastname: Krause
authors.forename: E
authors.initials: E
authors.lastname: Schäfer
authors.forename: M
authors.initials: M
authors.lastname: Frenzel
authors.forename: A
authors.initials: A
authors.lastname: Poetsch
authors.forename: S
authors.initials: S
authors.lastname: Rexroth
authors.forename: H J
authors.initials: HJ
authors.lastname: Schwassmann
authors.forename: T
authors.initials: T
authors.lastname: Suhai
authors.forename: J
authors.initials: J
authors.lastname: Vonck
authors.forename: N A
authors.initials: NA
authors.lastname: Dencher
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000544:Alzheimer Disease / Q000209:etiology* / Q000378:metabolism*; D025222:Chloroplast Proton-Translocating ATPases / Q000737:chemistry / Q000378:metabolism; D004734:Energy Metabolism; D006801:Humans; D008027:Light; D008565:Membrane Proteins / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000378:metabolism*; D008954:Models, Biological; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D010085:Oxidative Phosphorylation; D011522:Protons; D013185:Squalene / Q000031:analogs & derivatives / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D046912:Multiprotein Complexes; D011522:Protons; D014451:Ubiquinone; D013185:Squalene; D000255:Adenosine Triphosphate; D025222:Chloroplast Proton-Translocating ATPases; C024989:coenzyme Q10; C019556:squalane