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

Mühleip, A., Flygaard, R. K., Baradaran, R., Haapanen, O., Gruhl, T., Tobiasson, V., Maréchal, A., Sharma, V. and Amunts, A. (2023) Structural basis of mitochondrial membrane bending by the I–II–III2–IV2 supercomplex. Nature, 615(7954), pp. 934-938. (doi: 10.1038/s41586-023-05817-y) (PMID:36949187) (PMCID:PMC10060162)

Abstract

Mitochondrial energy conversion requires an intricate architecture of the inner mitochondrial membrane1. Here we show that a supercomplex containing all four respiratory chain components contributes to membrane curvature induction in ciliates. We report cryo-electron microscopy and cryo-tomography structures of the supercomplex that comprises 150 different proteins and 311 bound lipids, forming a stable 5.8-MDa assembly. Owing to subunit acquisition and extension, complex I associates with a complex IV dimer, generating a wedge-shaped gap that serves as a binding site for complex II. Together with a tilted complex III dimer association, it results in a curved membrane region. Using molecular dynamics simulations, we demonstrate that the divergent supercomplex actively contributes to the membrane curvature induction and tubulation of cristae. Our findings highlight how the evolution of protein subunits of respiratory complexes has led to the I–II–III2–IV2 supercomplex that contributes to the shaping of the bioenergetic membrane, thereby enabling its functional specialization.

• Item Type: Articles
• Additional Information: Open access funding provided by Stockholm University.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Muhleip, Dr Alexander
• Authors: Mühleip, A., Flygaard, R. K., Baradaran, R., Haapanen, O., Gruhl, T., Tobiasson, V., Maréchal, A., Sharma, V., and Amunts, A.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Nature
• Publisher: Nature Research
• ISSN: 0028-0836
• ISSN (Online): 1476-4687
• Published Online: 22 March 2023
• Copyright Holders: Copyright © 2023 The Authors
• First Published: First published in Nature 615(7954): 934-938
• Publisher Policy: Reproduced under a Creative Commons License