Article
Multidisciplinary Sciences
Eike Laube, Jakob Meier-Credo, Julian D. Langer, Werner Kuehlbrandt
Summary: The structure of mitochondrial complex I from Chaetomium thermophilum has been determined, revealing two distinct conformations and suggesting a universal mechanism of coupling electron transport to proton pumping.
Article
Biochemistry & Molecular Biology
Ahmed A. Noser, Aboubakr H. Abdelmonsef, Mohamed El-Naggar, Maha M. Salem
Summary: The study successfully synthesized novel amino acid Schiff base ligands and found that compounds 11 and 20 exhibited significant cytotoxic effects on cancer cells. These compounds showed activation of AMPK protein and oxidative stress, inhibition of mTOR protein, and blocking of hexokinase enzyme activity, demonstrating potential for cancer therapy.
Article
Plant Sciences
Agata Maziak, Malgorzata Heidorn-Czarna, Aleksandra Weremczuk, Hanna Janska
Summary: Research shows that in long-term moderate heat stress, Arabidopsis plants lacking mitochondrial proteases FTSH4 or OMA1 exhibit phenotypic changes associated with accumulation of small heat-shock proteins. The proteolytic activity of FTSH4 and OMA1 plays a crucial role in protecting mitochondrial proteins against aggregation under stress. Overall, the data suggest that FTSH4 and OMA1 increase plant tolerance to long-term moderate heat stress by reducing detergent-tolerant mitochondrial protein aggregation.
Article
Biochemistry & Molecular Biology
Mikhail A. Hameedi, Daniel N. Grba, Katherine H. Richardson, Andrew J. Y. Jones, Wei Song, Maxie M. Roessler, John J. Wright, Judy Hirst
Summary: The arginine residue R121 in respiratory complex I is crucial for the formation and stability of the iron-sulfur cluster N2, and mutations at this residue result in loss of enzyme activity. The mutation also leads to localized disorder in the nearby substrate-binding region, highlighting the importance of structural analysis for interpreting biochemical and spectroscopic data on complex I variants.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Caroline S. Pereira, Murilo H. Teixeira, David A. Russell, Judy Hirst, Guilherme M. Arantes
Summary: Respiratory complex I is an important cellular energy transducer in mitochondria. This study investigates the inhibition of complex I by rotenone and reveals the importance of ligand flexibility and conformer interconversion for efficient binding. Understanding the mechanism of rotenone action has implications for designing synthetic derivatives and further elucidating the catalytic mechanism of complex I.
SCIENTIFIC REPORTS
(2023)
Article
Oncology
Fang Han, Junwei Liu, Hongwu Chu, Dan Cao, Jia Wu, Hong Fu, Anyang Guo, Weiqin Chen, Yingping Xu, Xiangdong Cheng, Yuhua Zhang
Summary: The downregulation of NDUFC1 in HCC cells inhibits cell proliferation, arrests cell cycle, increases apoptosis, suppresses migration and invasion, and may promote tumor progression by multiple cancer-related pathways. NDUFC1 is associated with poor prognosis in HCC patients and could be a potential target for mitochondrial metabolism therapy.
FRONTIERS IN ONCOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Marta Vranas, Daniel Wohlwend, Danye Qiu, Stefan Gerhardt, Christian Trncik, Mehrosh Pervaiz, Kevin Ritter, Stefan Steimle, Antonio Randazzo, Oliver Einsle, Stefan Gunther, Henning J. Jessen, Alexander Kotlyar, Thorsten Friedrich
Summary: This study reports the specific action and structure of a novel inhibitor NADH-OH on respiratory complex I, revealing its regulatory role in mitochondrial ROS generation.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Cell Biology
Patrizia Bottoni, Alessandro Pontoglio, Salvatore Scara, Luisa Pieroni, Andrea Urbani, Roberto Scatena
Summary: Mitochondrial bioenergetics play an important role in pathophysiology, especially as unintended targets of different drugs. PPAR ligands, a class of drugs that activate Peroxisome Proliferator-Activated Receptors, were found to inhibit NADH coenzyme Q reductase and induce complex mitochondrial oxidative metabolism damage. This damage affects not only ATP synthesis but also respiratory control ratio, spare respiratory capacity, coupling efficiency, oxidative stress, and mitochondrial structural damage.
Article
Biochemistry & Molecular Biology
Karina Tuz, Ming Yuan, Yuyao Hu, Tien T. T. Do, Soohaeng Yoo Willow, Joseph A. DePaolo-Boisvert, James R. Fuller, David D. L. Minh, Oscar Juarez
Summary: The ion-pumping NQR complex is an essential respiratory enzyme in pathogenic bacteria, and it is the only enzyme reported to use riboflavin as a cofactor. This study identified the riboflavin-binding site in subunit B and found that conserved residues participate in stabilizing the cofactor through hydrogen bonds.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
John J. Wright, Olivier Biner, Injae Chung, Nils Burger, Hannah R. Bridges, Judy Hirst
Summary: This study demonstrates, for the first time, the reverse electron transfer (RET) through complex I in a synthetic proteoliposome system, and provides a complete kinetic characterization of RET catalysis. The researchers also reveal new mechanisms and physiological features of the reversibility of complex I catalysis by studying the regulation in mammalian enzyme and evaluating RET in other species.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Niklas Klusch, Jennifer Senkler, Oezkan Yildiz, Werner Kuehlbrandt, Hans-Peter Braun
Summary: Mitochondrial complex I is the main site for electron transfer and proton gradient generation. It is composed of two arms and a bridge domain, with different conformations and angles potentially regulating its activity.
Article
Genetics & Heredity
Alessandra Torraco, Alessia Nasca, Daniela Verrigni, Alessandra Pennisi, Maha S. Zaki, Giorgia Olivieri, Zahra Assouline, Diego Martinelli, Reza Maroofian, Teresa Rizza, Michela Di Nottia, Federica Invernizzi, Eleonora Lamantea, Daniela Longo, Henry Houlden, Holger Prokisch, Agnes Rotig, Carlo Dionisi-Vici, Enrico Bertini, Daniele Ghezzi, Rosalba Carrozzo, Daria Diodato
Summary: Isolated biochemical deficiency of mitochondrial complex I is commonly associated with a wide range of clinical symptoms, with Leigh syndrome being a frequent finding. This study identified novel NDUFA12 variants in seven patients from four unrelated families, with six presenting Leigh syndrome. Despite the absence of NDUFA12 protein in all patients, they exhibited different disease onset and clinical courses, highlighting the phenotypic variability associated with NDUFA12 defect.
Article
Biochemistry & Molecular Biology
Clara Lettl, Franziska Schindele, Ahmad Reza Mehdipour, Thomas Steiner, Diana Ring, Ruth Brack-Werner, Baerbel Stecher, Wolfgang Eisenreich, Ursula Bilitewski, Gerhard Hummer, Matthias Witschel, Wolfgang Fischer, Rainer Haas
Summary: Respiratory complex I plays an important role in cellular respiration of both eukaryotic cells and bacteria. The inhibition of complex I by mitochondrial complex I inhibitors can selectively kill Helicobacter pylori, a Gram-negative bacterial pathogen, while leaving other bacteria unaffected. The unique composition of the quinone-binding pocket in H. pylori complex I is responsible for this hypersensitivity, suggesting the potential of developing complex I inhibitors as narrow-spectrum antimicrobial agents against H. pylori.
CELL CHEMICAL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Jiao Li, Long Han, Francesca Vallese, Ziqiao Ding, Sylvia K. Choi, Sangjin Hong, Yanmei Luo, Bin Liu, Chun Kit Chan, Emad Tajkhorshid, Jiapeng Zhu, Oliver Clarke, Kai Zhang, Robert Gennis
Summary: Two independent structures of the proton-pumping, respiratory cytochrome bo(3) ubiquinol oxidase have been determined by cryogenic electron microscopy in nanodiscs, showing metal redox centers, redox-active cofactors, water molecules, and ubiquinone-8 in the substrate binding site, with isoprene side chain clamped within a hydrophobic groove in subunit I. Both structures demonstrate dynamics of residue H98(I) facilitating proton transfer from ubiquinol during substrate oxidation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Teri N. Hreha, Sara Foreman, Ana Duran-Pinedo, Andrew R. Morris, Patricia Diaz-Rodriguez, J. Andrew Jones, Kristina Ferrara, Anais Bourges, Lauren Rodriguez, Mattheos A. G. Koffas, Mariah Hahn, Alan R. Hauser, Blanca Barquera
Summary: Pseudomonas aeruginosa is an opportunistic pathogen with a highly adaptable metabolism, using multiple enzymes to achieve broad pathogenesis. Mutations in specific genes can impact biofilm formation, pyocyanin production, and efficiency in killing host cells.
Article
Microbiology
Adam Maynard, Nicole L. Butler, Takeshi Ito, Adilson Jose da Silva, Masatoshi Murai, Tsute Chen, Mattheos A. G. Koffas, Hideto Miyoshi, Blanca Barquera
JOURNAL OF BACTERIOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Shinpei Uno, Takahiro Masuya, Kyoko Shinzawa-Itoh, Jonathan Lasham, Outi Haapanen, Tomoo Shiba, Daniel Ken Inaoka, Vivek Sharma, Masatoshi Murai, Hideto Miyoshi
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Review
Biochemistry & Molecular Biology
Masatoshi Murai
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
(2020)
Article
Biochemistry & Molecular Biology
Atsuhito Tsuji, Takumi Akao, Takahiro Masuya, Masatoshi Murai, Hideto Miyoshi
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Article
Multidisciplinary Sciences
Kento Tsukada, Shono Shinki, Akiho Kaneko, Kazuma Murakami, Kazuhiro Irie, Masatoshi Murak, Hideto Miyoshi, Shingo Dan, Kumi Kawaji, Hironori Hayashi, Eiichi N. Kodama, Aki Hori, Emil Salim, Takayuki Kuraishi, Naoya Hirata, Yasunari Kanda, Teigo Asai
NATURE COMMUNICATIONS
(2020)
Article
Biochemistry & Molecular Biology
Takahiro Masuya, Yuki Sano, Hinako Tanaka, Nicole L. Butler, Takeshi Ito, Tatsuhiko Tosaki, Joel E. Morgan, Masatoshi Murai, Blanca Barquera, Hideto Miyoshi
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Article
Biochemistry & Molecular Biology
Takahiro Masuya, Shinpei Uno, Masatoshi Murai, Hideto Miyoshi
Summary: The study provides direct evidence that the quinone reaction cavity is accessible from the proposed matrix-side region covered by the ND3 TMH1-2 loop, despite initial doubts regarding the accessibility of the cavity from this region.
Article
Biochemistry & Molecular Biology
Moe Ishikawa, Takahiro Masuya, Hinako Tanaka, Wataru Aoki, Noam Hantman, Nicole L. Butler, Masatoshi Murai, Blanca Barquera, Hideto Miyoshi
Summary: The study focused on modifying a specific lysine residue on the NqrB subunit of the Na+-pumping NADH-ubiquinone oxidoreductase in Vibrio cholerae to investigate its unknown structure and function. The researchers successfully achieved the specific modification and gained valuable information about the positioning of the nonmodeled region of NqrB, suggesting its potential orientation towards the membrane phase for regulating the ubiquinone reaction in the adjacent NqrA.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
(2021)
Article
Biotechnology & Applied Microbiology
Katsuyuki Sakai, Yufu Unten, Aoi Kimishima, Kenichi Nonaka, Takumi Chinen, Kazunari Sakai, Takeo Usui, Kazuro Shiomi, Masato Iwatsuki, Masatoshi Murai, Hideto Miyoshi, Yukihiro Asami, Satoshi Omura
Summary: The study identified two new tetramic acid derivatives, traminines A (1) and B (2), isolated from a culture broth of Fusarium concentricum FKI-7550, with their chemical structures elucidated by NMR studies. The compounds were found to inhibit the growth of a multidrug-sensitive yeast strain by targeting enzymes involved in oxidative phosphorylation in yeast mitochondria. Compound 1 was found to inhibit both complex III and FoF1-ATPase, while compound 2 solely inhibited complex III.
JOURNAL OF INDUSTRIAL MICROBIOLOGY & BIOTECHNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yufu Unten, Masatoshi Murai, Tomoki Koshitaka, Kotaro Kitao, Osamu Shirai, Takahiro Masuya, Hideto Miyoshi
Summary: Tamoxifen has been widely used for ER-positive breast cancer treatment, and exhibits ER-independent anticancer effects. It has been suggested that tamoxifen induces apoptosis through mitochondrial dysfunction. However, the mechanism of action of tamoxifen at the isolated mitochondrial level is not fully understood. This study found that tamoxifen has the potential to inhibit both respiratory complex I and ATP synthase in isolated rat liver mitochondria, and may suppress opening of the mitochondrial permeability transition pore.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
(2022)
Article
Biochemistry & Molecular Biology
Moe Ishikawa, Takahiro Masuya, Seina Kuroda, Shinpei Uno, Nicole L. Butler, Sara Foreman, Masatoshi Murai, Blanca Barquera, Hideto Miyoshi
Summary: This study investigates the mechanism of Na+-pumping NADH-ubiquinone oxidoreductase and reveals the critical role of the side chain of UQ in Na+ translocation.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
(2022)
Article
Biochemistry & Molecular Biology
Daniel N. Grba, James N. Blaza, Hannah R. Bridges, Ahmed-Noor A. Agip, Zhan Yin, Masatoshi Murai, Hideto Miyoshi, Judy Hirst
Summary: Mitochondrial complex I is a crucial enzyme in energy metabolism and plays a key role in ATP synthesis. This study reveals the structure of mouse complex I with a tight-binding acetogenin inhibitor, providing insights into the binding mode and structure-activity relationships. The amphipathic nature of the channel supports both tight binding of the inhibitor and rapid exchange of the substrate and product.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Shinpei Uno, Takahiro Masuya, Oleksii Zdorevskyi, Ryo Ikunishi, Kyoko Shinzawa-Itoh, Jonathan Lasham, Vivek Sharma, Masatoshi Murai, Hideto Miyoshi
Summary: The reduction of ubiquinone (UQ) by NADH-UQ oxidoreductase plays a crucial role in proton translocation across the inner mitochondrial membrane. This study demonstrates that the access of oversized UQs to the reaction site is obstructed in the isolated enzyme, possibly due to alterations in the access route caused by detergent solubilization. Furthermore, the reduction behaviors of different pUQ sizes varied between the isolated and native enzymes, suggesting that the canonical UQ tunnel model cannot fully explain these observations.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Jun-ichi Kishikawa, Moe Ishikawa, Takahiro Masuya, Masatoshi Murai, Yuki Kitazumi, Nicole L. Butler, Takayuki Kato, Blanca Barquera, Hideto Miyoshi
Summary: The Na+-pumping NADH-ubiquinone oxidoreductase (Na+-NQR) is a unique respiratory enzyme found in many pathogenic bacteria. In this study, high-resolution cryo-EM structures of Na+-NQR from V. cholerae with or without a bound inhibitor are presented, revealing the arrangement of all redox cofactors and the presence of a 2Fe-2S cluster. The study also demonstrates the high flexibility of NqrF and the binding of specific inhibitors to the N-terminal region of NqrB.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Yufu Unten, Masatoshi Murai, Katsuyuki Sakai, Yukihiro Asami, Takenori Yamamoto, Takahiro Masuya, Hideto Miyoshi
Summary: Fusaramin, a 3-acyl tetramic acid isolated from Fusarium concentricum FKI-7550, is an inhibitor of oxidative phosphorylation in Saccharomyces cerevisiae mitochondria by impairing VDAC1 functions. In addition, it also inhibits FoF1-ATP synthase and complex III at higher concentrations.
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
(2021)