Structure of Escherichia coli respiratory complex I reconstituted into lipid nanodiscs reveals an uncoupled conformation

Kolata, P.; Efremov, Rouslan G.

doi:10.1016/j.bbabio.2022.148638

Cited by 2 publications

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“…1). This originally unexpected and disputed finding was fully corroborated by the subsequent structures of complex I solved by X-ray diffraction and more recently by cryoelectron microscopy (cryoEM) [4][5][6][7][8]. Moreover, the structural work revealed that the binding site of Q, near the Fe/S centre N2, resides in a long tunnel leading from the membrane domain into the hydrophilic part circa 30 Å away from the membrane proper (Fig.…”

mentioning

confidence: 74%

“…Moreover, it is also not clear how the two negative charges (or proton holes) remain deprotonated for hundreds of microseconds to milliseconds until neutralised. Based on static structural data, the Q cavity has been proposed to be fully isolated from the solvent in order to prevent loss of energy [66], but only to open in certain catalytic states to allow binding/unbinding of Q (see [8,67]). Some suggestions based on MD simulations have also been put forward, where a conserved arginine residue stabilises the deprotonated tyrosine-144 [28] (see also [68]), which may prevent its rapid protonation from the bulk N phase.…”

Section: Other Proposed Proton-translocation Mechanismsmentioning

confidence: 99%

“…Its redox activity is linked to pumping of four protons (per 2 electrons or one NADH oxidised) across the inner membrane of mitochondria [1][2][3] or the bacterial cell membrane. Bacterial complex I is structurally much simpler than its mitochondrial counterpart [4][5][6][7][8], but the two share a basic L-shaped structure, where the domain catalysing NADH oxidation by ubiquinone protrudes into the negatively charged aqueous N-side of the membrane, whereas proton translocation is catalysed by the membrane domain (Fig. 1).…”

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confidence: 99%

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On the role of ubiquinone in the proton translocation mechanism of respiratory complex I

2022

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Complex I converts oxidoreduction energy into a proton electrochemical gradient across the inner mitochondrial or bacterial cell membrane. This gradient is the primary source of energy for aerobic synthesis of ATP. Oxidation of reduced nicotinamide adenine dinucleotide (NADH) by ubiquinone (Q) yields NAD + and ubiquinol (QH 2 ), which is tightly coupled to translocation of four protons from the negatively to the positively charged side of the membrane. Electrons from NADH oxidation reach the iron-sulfur centre N2 positioned near the bottom of a tunnel that extends circa 30 Å from the membrane domain into the hydrophilic domain of the complex. The tunnel is occupied by ubiquinone, which can take a distal position near the N2 centre or proximal positions closer to the membrane. Here, we review important structural, kinetic and thermodynamic properties of ubiquinone that define its role in complex I function. We suggest that this function exceeds that of a mere substrate or electron acceptor and propose that ubiquinone may be the redox element of complex I coupling electron transfer to proton translocation.

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confidence: 74%

Section: Other Proposed Proton-translocation Mechanismsmentioning

confidence: 99%

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confidence: 99%

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On the role of ubiquinone in the proton translocation mechanism of respiratory complex I

2022

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“…We identified PSST as a substrate of FTSH3. PSST, an orthologue of human NDUFS7, is a 20 kD Q module subunit that is located within the interface of the matrix and membrane arms domain and is conserved across species (Fiedorczuk et al, 2016;Klusch et al, 2021;Baradaran et al, 2013;Kolata and Efremov, 2021) (Figure S4). Mutation of PSST conserved loop residues in aerobic yeast Yarrowia lypolitica resulted in reduced electron transfer to ubiquinone (Galemou Yoga et al, 2019), whilst deletion of PSST in Arabidopsis results in severe developmental delays confirming its essential function .…”

Section: Discussionmentioning

confidence: 99%

FTSH3 facilitates complex I degradation through a direct interaction with the complex I subunit PSST

Ghifari

Ivanova

Berkowitz

et al. 2023

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Complex I (NADH dehydrogenase), the largest complex involved in mitochondrial oxidative phosphorylation is composed of nuclear and mitochondrial encoded subunits. Its assembly requires sequential addition of subdomains and modules. As it is prone to oxidative damage, complex I subunits continually undergo proteolysis and turnover. We describe the mechanism by which complex I abundance is regulated in a complex I deficient mutant. Using a forward genetic approach we have identified that the complex I Q-module domain subunit PSST, interacts with FTSH3 (Filamentous Temperature Sensitive H3) to mediate the disassembly of the matrix arm domain module for proteolysis and turnover as a means of protein quality control. We show the direct interaction of FTSH3 with PSST and identify the amino acid residues required for this interaction. It is the ATPase function of FTSH3 that is required for the interaction, as the mutation can be compensated by a proteolytically inactive form of FTSH3. Furthermore, it cannot be compensated by FTSH10 that is also located in mitochondria, as the latter does not interact with PSST. This study reveals the mechanistic process at the resolution of the residues involved of how FTSH3 recognises complex I for degradation.

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Structure of Escherichia coli respiratory complex I reconstituted into lipid nanodiscs reveals an uncoupled conformation

Cited by 2 publications

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On the role of ubiquinone in the proton translocation mechanism of respiratory complex I

On the role of ubiquinone in the proton translocation mechanism of respiratory complex I

FTSH3 facilitates complex I degradation through a direct interaction with the complex I subunit PSST

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