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Title: Natural tetramic acids elicit multiple inhibitory actions against mitochondrial machineries presiding over oxidative phosphorylation
Authors: Unten, Yufu
Murai, Masatoshi  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0001-6601-2854 (unconfirmed)
Sakai, Katsuyuki
Asami, Yukihiro
Yamamoto, Takenori
Masuya, Takahiro
Miyoshi, Hideto
Author's alias: 運天, 優歩
村井, 正俊
桝谷, 貴洋
三芳, 秀人
Keywords: tetramic acid
fusaramin
mitochondria
oxidative phosphorylation
VDAC1
Issue Date: Dec-2021
Publisher: Oxford University Press (OUP)
Journal title: Bioscience, Biotechnology, and Biochemistry
Volume: 85
Issue: 12
Start page: 2368
End page: 2377
Abstract: The mitochondrial machineries presiding over ATP synthesis via oxidative phosphorylation are promising druggable targets. Fusaramin, a 3-acyl tetramic acid isolated from Fusarium concentricum FKI-7550, is an inhibitor of oxidative phosphorylation in Saccharomyces cerevisiae mitochondria, although its target has yet to be identified. Fusaramin significantly interfered with [³H]ADP uptake by yeast mitochondria at the concentration range inhibiting oxidative phosphorylation. A photoreactive fusaramin derivative (pFS-5) specifically labeled voltage-dependent anion channel 1 (VDAC1), which facilitates trafficking of ADP/ATP across the outer mitochondrial membrane. These results strongly suggest that the inhibition of oxidative phosphorylation by fusaramin is predominantly attributable to the impairment of VDAC1 functions. Fusaramin also inhibited F₀F₁ATP synthase and ubiquinol-cytochrome c oxidoreductase (complex III) at concentrations higher than those required for the VDAC inhibition. Considering that other tetramic acid derivatives are reported to inhibit F₀F₁ATP synthase and complex III, natural tetramic acids were found to elicit multiple inhibitory actions against mitochondrial machineries.
Rights: This is a pre-copyedited, author-produced version of an article accepted for publication in [Bioscience, Biotechnology, and Biochemistry] following peer review. The version of record [Yufu Unten, Masatoshi Murai, Katsuyuki Sakai, Yukihiro Asami, Takenori Yamamoto, Takahiro Masuya, Hideto Miyoshi, Natural tetramic acids elicit multiple inhibitory actions against mitochondrial machineries presiding over oxidative phosphorylation, Bioscience, Biotechnology, and Biochemistry, Volume 85, Issue 12, December 2021, Pages 2368–2377] is available online at: https://doi.org/10.1093/bbb/zbab176.
The full-text file will be made open to the public on 08 October 2022 in accordance with publisher's 'Terms and Conditions for Self-Archiving'.
This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。
URI: http://hdl.handle.net/2433/266256
DOI(Published Version): 10.1093/bbb/zbab176
PubMed ID: 34625801
Appears in Collections:Journal Articles

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