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ND3 Cys39 in complex I is exposed during mitochondrial respiration

Lookup NU author(s): Dr Kurt Hoogewijs

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

© 2021 The Author(s). Mammalian complex I can adopt catalytically active (A-) or deactive (D-) states. A defining feature of the reversible transition between these two defined states is thought to be exposure of the ND3 subunit Cys39 residue in the D-state and its occlusion in the A-state. As the catalytic A/D transition is important in health and disease, we set out to quantify it by measuring Cys39 exposure using isotopic labeling and mass spectrometry, in parallel with complex I NADH/CoQ oxidoreductase activity. To our surprise, we found significant Cys39 exposure during NADH/CoQ oxidoreductase activity. Furthermore, this activity was unaffected if Cys39 alkylation occurred during complex I-linked respiration. In contrast, alkylation of catalytically inactive complex I irreversibly blocked the reactivation of NADH/CoQ oxidoreductase activity by NADH. Thus, Cys39 of ND3 is exposed in complex I during mitochondrial respiration, with significant implications for our understanding of the A/D transition and the mechanism of complex I.

Publication metadata

Author(s): Burger N, James AM, Mulvey JF, Hoogewijs K, Ding S, Fearnley IM, Loureiro-Lopez M, Norman AAI, Arndt S, Mottahedin A, Sauchanka O, Hartley RC, Krieg T, Murphy MP

Publication type: Article

Publication status: Published

Journal: Cell Chemical Biology

Year: 2022

Volume: 29

Issue: 4

Pages: 636-649

Print publication date: 21/04/2022

Online publication date: 04/11/2021

Acceptance date: 07/10/2021

Date deposited: 10/05/2022

ISSN (print): 2451-9456

ISSN (electronic): 2451-9448

Publisher: Cell Press

URL: https://doi.org/10.1016/j.chembiol.2021.10.010

DOI: 10.1016/j.chembiol.2021.10.010

PubMed id: 34739852

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