Open AccessDeactivation blocks proton pathways in the mitochondrial complex I
Author(s) -
Michael Röpke,
Daniel Riepl,
Patricia Saura,
Andrea Di Luca,
Max E. Mühlbauer,
Alexander Jussupow,
Ana P. GámizHernández,
Ville R. I. Kaila
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2019498118
Subject(s) - electrochemical gradient , biophysics , transmembrane protein , proton pump , transmembrane domain , conformational change , chemistry , protein structure , proton , electron transfer , membrane , biochemistry , biology , photochemistry , atpase , enzyme , receptor , physics , quantum mechanics
Significance The electron transport chain of mitochondria is initiated by the respiratory complex I that converts chemical energy into a proton motive force to power synthesis of adenosine triphosphate. On a chemical level, complex I catalyzes elementary electron and proton transfer processes that couple across large molecular distances of >300 Å. However, under low oxygen concentrations, the respiratory chain operates in reverse mode and produces harmful reactive oxygen species. To avoid cell damage, the mitochondrial complex I transitions into a deactive state that inhibits turnover by molecular principles that remain elusive. By combining large-scale molecular simulations with cryo-electron microscopy data, we show here that complex I deactivation blocks the communication between proton pumping and redox modules by conformational and hydration changes.