TY - JOUR A1 - Sousa, Joana Sofia de A1 - Mills, Deryck J. A1 - Vonck, Janet A1 - Kühlbrandt, Werner T1 - Functional asymmetry and electron flow in the bovine respirasome T2 - eLife N2 - Respirasomes are macromolecular assemblies of the respiratory chain complexes I, III and IV in the inner mitochondrial membrane. We determined the structure of supercomplex I1III2IV1 from bovine heart mitochondria by cryo-EM at 9 Å resolution. Most protein-protein contacts between complex I, III and IV in the membrane are mediated by supernumerary subunits. Of the two Rieske iron-sulfur cluster domains in the complex III dimer, one is resolved, indicating that this domain is immobile and unable to transfer electrons. The central position of the active complex III monomer between complex I and IV in the respirasome is optimal for accepting reduced quinone from complex I over a short diffusion distance of 11 nm, and delivering reduced cytochrome c to complex IV. The functional asymmetry of complex III provides strong evidence for directed electron flow from complex I to complex IV through the active complex III monomer in the mammalian supercomplex. KW - Research article KW - Biophysics and structural biology KW - Bos taurus KW - Cryo-em KW - Mitochondria KW - Respiratory chain KW - Supercomplex Y1 - 2017 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/45001 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-450019 SN - 2050-084X N1 - Copyright Sousa et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. VL - 5 IS - e21290 SP - 1 EP - 17 PB - eLife Sciences Publications CY - Cambridge ER -