Structures of Respiratory Supercomplex I+III Reveal Functional and Conformational Crosstalk

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2019 Sep 8

PMID 31492636

Citations 87

Authors

James A Letts

Karol Fiedorczuk

Gianluca Degliesposti

Mark Skehel

Leonid A Sazanov

Affiliations

Soon will be listed here.

Abstract

The mitochondrial electron transport chain complexes are organized into supercomplexes (SCs) of defined stoichiometry, which have been proposed to regulate electron flux via substrate channeling. We demonstrate that CoQ trapping in the isolated SC I+III limits complex (C)I turnover, arguing against channeling. The SC structure, resolved at up to 3.8 Å in four distinct states, suggests that CoQ oxidation may be rate limiting because of unequal access of CoQ to the active sites of CIII. CI shows a transition between "closed" and "open" conformations, accompanied by the striking rotation of a key transmembrane helix. Furthermore, the state of CI affects the conformational flexibility within CIII, demonstrating crosstalk between the enzymes. CoQ was identified at only three of the four binding sites in CIII, suggesting that interaction with CI disrupts CIII symmetry in a functionally relevant manner. Together, these observations indicate a more nuanced functional role for the SCs.

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