Osm1 facilitates the transfer of electrons from Erv1 to fumarate in the redox-regulated import pathway in the mitochondrial intermembrane space

Neal, Sonya E.; Dabir, Deepa V.; Wijaya, Juwina; Boon, Cennyana; Koehler, Carla M.

doi:10.1091/mbc.e16-10-0712

Cited by 32 publications

(29 citation statements)

References 76 publications

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“…Both of these peroxidase enzymes were shown to interact with components of the MIA machinery directly, thus they can scavenge hydrogen peroxide produced from the MIA pathway effectively. Moreover, a recent study showed that yeast Erv1 can also transfer electrons to the IMS localised fumarate reductase Osm1, and via Osm1 transfer electrons to fumarate under both aerobic and anaerobic conditions . Thus, yeast can exploit diverse electron acceptors for MIA pathway in the IMS, with at least three electron acceptors, oxygen, cytochrome c and Osm1/fumarate, have been identified.…”

Section: Discussionmentioning

confidence: 99%

Kinetic characterisation of Erv1, a key component for protein import and folding in yeast mitochondria

et al. 2019

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Yeast (Saccharomyces cerevisiae) essential for respiration and viability 1 (Erv1; EC number http://www.chem.qmul.ac.uk/iubmb/enzyme/1/8/3/2.html), a member of the flavin adenine dinucleotide‐dependent Erv1/ALR disulphide bond generating enzyme family, works together with Mia40 to catalyse protein import and oxidative folding in the mitochondrial intermembrane space. Erv1/ALR functions either as an oxidase or cytochrome c reductase by passing electrons from a thiol substrate to molecular oxygen (O2) or cytochrome c, respectively. However, the substrate specificity for oxygen and cytochrome c is not fully understood. In this study, the oxidase and cytochrome c reductase kinetics of yeast Erv1 were investigated in detail, under aerobic and anaerobic conditions, using stopped‐flow absorption spectroscopy and oxygen consumption analysis. Using DTT as an electron donor, our results show that cytochrome c is ~ 7‐ to 15‐fold more efficient than O2 as electron acceptors for yeast Erv1, and that O2 is a competitive inhibitor of Erv1 cytochrome c reductase activity. In addition, Mia40, the physiological thiol substrate of Erv1, was used as an electron donor for Erv1 in a detailed enzyme kinetic study. Different enzyme kinetic kcat and Km values were obtained with Mia40 compared to DTT, suggesting that Mia40 modulates Erv1 enzyme kinetics. Taken together, this study shows that Erv1 is a moderately active enzyme with the ability to use both O2 and cytochrome c as the electron acceptors, indicating that Erv1 contributes to mitochondrial hydrogen peroxide production. Our results also suggest that Mia40‐Erv1 system may involve in regulation of the redox state of glutathione in the mitochondrial intermembrane space. Erv1 EC number http://www.chem.qmul.ac.uk/iubmb/enzyme/1/8/3/2.html.

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Section: Discussionmentioning

confidence: 99%

Kinetic characterisation of Erv1, a key component for protein import and folding in yeast mitochondria

et al. 2019

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“…This is an important difference as the cytochrome c pathway ends up with the production of H 2 O after a relay by cytochrome oxidase whereas a direct reaction with oxygen implies H 2 O 2 production. In yeast grown in anaerobic conditions, electrons can be transferred to the Osm1/fumarate couple in the mitochondrial intermembrane space (Neal et al ., ).…”

Section: The Disulfide Relay In the Mitochondrial Intermembrane Spacementioning

confidence: 99%

Oxidative protein folding: state‐of‐the‐art and current avenues of research in plants

2018

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Contents Summary I. Introduction II. Formation and isomerization of disulfides in the ER and the Golgi apparatus III. The disulfide relay in the mitochondrial intermembrane space: why are plants different? IV. Disulfide bond formation on luminal proteins in thylakoids V. Conclusion Acknowledgements References SUMMARY: Disulfide bonds are post-translational modifications crucial for the structure and function of thousands of proteins. Their formation and isomerization, referred to as oxidative folding, require specific protein machineries found in oxidizing subcellular compartments, namely the endoplasmic reticulum and the associated endomembrane system, the intermembrane space of mitochondria and the thylakoid lumen of chloroplasts. At least one protein component is required for transferring electrons from substrate proteins to an acceptor that is usually molecular oxygen. For oxidation reactions, incoming reduced substrates are oxidized by thiol-oxidoreductase proteins (or domains in case of chimeric proteins), which are usually themselves oxidized by a single thiol oxidase, the enzyme generating disulfide bonds de novo. By contrast, the description of the molecular actors and pathways involved in proofreading and isomerization of misfolded proteins, which require a tightly controlled redox balance, lags behind. Herein we provide a general overview of the knowledge acquired on the systems responsible for oxidative protein folding in photosynthetic organisms, highlighting their particularities compared to other eukaryotes. Current research challenges are discussed including the importance and specificity of these oxidation systems in the context of the existence of reducing systems in the same compartments.

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“…Erv1 can either directly reduce oxygen to hydrogen peroxide or use cytochrome c as an electron acceptor (Figure 3 ). Alternatively, it can interact with the fumarate reductase Osm1 in order to get re-oxidized under anaerobic conditions (Neal et al, 2017 ).…”

Section: The Mitochondrial Disulfide Relaymentioning

confidence: 99%

Protein Translocation into the Intermembrane Space and Matrix of Mitochondria: Mechanisms and Driving Forces

Backes

Herrmann

2017

Front. Mol. Biosci.

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Mitochondria contain two aqueous subcompartments, the matrix and the intermembrane space (IMS). The matrix is enclosed by both the inner and outer mitochondrial membranes, whilst the IMS is sandwiched between the two. Proteins of the matrix are synthesized in the cytosol as preproteins, which contain amino-terminal matrix targeting sequences that mediate their translocation through translocases embedded in the outer and inner membrane. For these proteins, the translocation reaction is driven by the import motor which is part of the inner membrane translocase. The import motor employs matrix Hsp70 molecules and ATP hydrolysis to ratchet proteins into the mitochondrial matrix. Most IMS proteins lack presequences and instead utilize the IMS receptor Mia40, which facilitates their translocation across the outer membrane in a reaction that is coupled to the formation of disulfide bonds within the protein. This process requires neither ATP nor the mitochondrial membrane potential. Mia40 fulfills two roles: First, it acts as a holdase, which is crucial in the import of IMS proteins and second, it functions as a foldase, introducing disulfide bonds into newly imported proteins, which induces and stabilizes their natively folded state. For several Mia40 substrates, oxidative folding is an essential prerequisite for their assembly into oligomeric complexes. Interestingly, recent studies have shown that the two functions of Mia40 can be experimentally separated from each other by the use of specific mutants, hence providing a powerful new way to dissect the different physiological roles of Mia40. In this review we summarize the current knowledge relating to the mitochondrial matrix-targeting and the IMS-targeting/Mia40 pathway. Moreover, we discuss the mechanistic properties by which the mitochondrial import motor on the one hand and Mia40 on the other, drive the translocation of their substrates into the organelle. We propose that the lateral diffusion of Mia40 in the inner membrane and the oxidation-mediated folding of incoming polypeptides supports IMS import.

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Osm1 facilitates the transfer of electrons from Erv1 to fumarate in the redox-regulated import pathway in the mitochondrial intermembrane space

Cited by 32 publications

References 76 publications

Kinetic characterisation of Erv1, a key component for protein import and folding in yeast mitochondria

Kinetic characterisation of Erv1, a key component for protein import and folding in yeast mitochondria

Oxidative protein folding: state‐of‐the‐art and current avenues of research in plants

Protein Translocation into the Intermembrane Space and Matrix of Mitochondria: Mechanisms and Driving Forces

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