Oversized ubiquinones as molecular probes for structural dynamics of the ubiquinone reaction site in mitochondrial respiratory complex I

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Uno , S , Masuya , T , Shinzawa-Itoh , K , Lasham , J , Haapanen , O , Shiba , T , Inaoka , D K , Sharma , V , Murai , M & Miyoshi , H 2020 , ' Oversized ubiquinones as molecular probes for structural dynamics of the ubiquinone reaction site in mitochondrial respiratory complex I ' , Journal of Biological Chemistry , vol. 295 , no. 8 , pp. 2449-2463 . https://doi.org/10.1074/jbc.RA119.012347

Title: Oversized ubiquinones as molecular probes for structural dynamics of the ubiquinone reaction site in mitochondrial respiratory complex I
Author: Uno, Shinpei; Masuya, Takahiro; Shinzawa-Itoh, Kyoko; Lasham, Jonathan; Haapanen, Outi; Shiba, Tomoo; Inaoka, Daniel Ken; Sharma, Vivek; Murai, Masatoshi; Miyoshi, Hideto
Other contributor: University of Helsinki, Materials Physics
University of Helsinki, Materials Physics
University of Helsinki, Department of Physics


Date: 2020-02-21
Language: eng
Number of pages: 15
Belongs to series: Journal of Biological Chemistry
ISSN: 0021-9258
DOI: https://doi.org/10.1074/jbc.RA119.012347
URI: http://hdl.handle.net/10138/321715
Abstract: NADH-quinone oxidoreductase (complex I) couples electron transfer from NADH to quinone with proton translocation across the membrane. Quinone reduction is a key step for energy transmission from the site of quinone reduction to the remotely located proton-pumping machinery of the enzyme. Although structural biology studies have proposed the existence of a long and narrow quinone-access channel, the physiological relevance of this channel remains debatable. We investigated here whether complex I in bovine heart submitochondrial particles (SMPs) can catalytically reduce a series of oversized ubiquinones (OS-UQs), which are highly unlikely to transit the narrow channel because their side chain includes a bulky ?block? that is ?13 ? across. We found that some OS-UQs function as efficient electron acceptors from complex I, accepting electrons with an efficiency comparable with ubiquinone-2. The catalytic reduction and proton translocation coupled with this reduction were completely inhibited by different quinone-site inhibitors, indicating that the reduction of OS-UQs takes place at the physiological reaction site for ubiquinone. Notably, the proton-translocating efficiencies of OS-UQs significantly varied depending on their side-chain structures, suggesting that the reaction characteristics of OS-UQs affect the predicted structural changes of the quinone reaction site required for triggering proton translocation. These results are difficult to reconcile with the current channel model; rather, the access path for ubiquinone may be open to allow OS-UQs to access the reaction site. Nevertheless, contrary to the observations in SMPs, OS-UQs were not catalytically reduced by isolated complex I reconstituted into liposomes. We discuss possible reasons for these contradictory results.
Subject: bioenergetics
mitochondria
complex I
ubiquinone
chemical biology
respiratory chain
proton pump
PINPOINT CHEMICAL-MODIFICATION
49 KDA
CRYSTAL-STRUCTURE
INNER MEMBRANE
PROTON PUMP
NADH
REDUCTION
OXIDOREDUCTASE
MECHANISM
BINDING
1182 Biochemistry, cell and molecular biology
114 Physical sciences
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