Structural basis of mitochondrial membrane bending by I-II-III2-IV2 supercomplex

Abstract

Mitochondrial energy conversion requires an intricate architecture of the inner 23 mitochondrial membrane1. Here we show that in ciliates, the membrane curvature is 24 provided by a supercomplex containing all four respiratory chain components. We report 25 cryo-electron microscopy and cryo-tomography structures of the supercomplex that 26 comprises 150 different proteins and 311 bound lipids, forming a stable 5.8-megadalton 27 assembly. Due to subunit acquisition and extension, complex I associates with a complex IV 28 dimer, generating a wedge-shaped gap that serves as a binding site for complex II. 29 Together with a tilted complex III dimer association, it results in a curved membrane 30 region. Using molecular dynamics simulations, we demonstrate that the divergent 31 supercomplex actively contributes to the membrane curvature induction and cristae 32 tubulation. Our findings explain how the architecture of the native I-II-III2-IV2 33 supercomplex reflects the functional specialization of bioenergetics by shaping the 34 membrane.