Structure of respiratory complex I: “Minimal” bacterial and “de luxe” mammalian versions Book Section


Author(s): Sazanov, Leonid A
Article/Chapter Title: Structure of respiratory complex I: “Minimal” bacterial and “de luxe” mammalian versions
Affiliation IST Austria
Abstract: Complex I (NADH:ubiquinone oxidoreductase) plays a central role in cellular energy generation, contributing to the proton motive force used to produce ATP. It couples the transfer of two electrons between NADH and quinone to translocation of four protons across the membrane. It is the largest protein assembly of bacterial and mitochondrial respiratory chains, composed, in mammals, of up to 45 subunits with a total molecular weight of ∼1 MDa. Bacterial enzyme is about half the size, providing the important “minimal” model of complex I. The l-shaped complex consists of a hydrophilic arm, where electron transfer occurs, and a membrane arm, where proton translocation takes place. Previously, we have solved the crystal structures of the hydrophilic domain of complex I from Thermus thermophilus and of the membrane domain from Escherichia coli, followed by the atomic structure of intact, entire complex I from T. thermophilus. Recently, we have solved by cryo-EM a first complete atomic structure of mammalian (ovine) mitochondrial complex I. Core subunits are well conserved from the bacterial version, whilst supernumerary subunits form an interlinked, stabilizing shell around the core. Subunits containing additional cofactors, including Zn ion, NADPH and phosphopantetheine, probably have regulatory roles. Dysfunction of mitochondrial complex I is implicated in many human neurodegenerative diseases. The structure of mammalian enzyme provides many insights into complex I mechanism, assembly, maturation and dysfunction, allowing detailed molecular analysis of disease-causing mutations.
Book Title: Mechanisms of primary energy transduction in biology
ISBN: 978-1-78801-363-5
Publisher: Royal Society of Chemistry  
Date Published: 2017-11-29
Start Page: 25
End Page: 59
DOI: 10.1039/9781788010405-00025
Open access: no
IST Austria Authors
  1. Leonid Sazanov
    51 Sazanov