Mitochondrial and endoplasmic reticulum redox biology
in health and diseas
Publications
2021
Bonnefoy, Nathalie and Claire Remacle. 2021 in press. Biolistic transformation of Chlamydomonas reinhardtii and Saccharomyces cerevisiae mitochondria. In Methods in Mol. Biol., Nicholls, T. Uhler J. et Falkenberg M. (eds), Humana Press Inc., Totowa.
Mounkoro, Pierre, Thomas Michel, and Brigitte Meunier. 2021. “Revisiting the Mode of Action of the Antimalarial Proguanil Using the Yeast Model.” Biochemical and Biophysical Research Communications 534 (January): 94–98. https://doi.org/10.1016/j.bbrc.2020.12.004.
Mounkoro, Pierre, Thomas Michel, Marie-Pierre Golinelli-Cohen, Stéphanie Blandin, Elisabeth Davioud-Charvet, and Brigitte Meunier. 2021. “A Role for the Succinate Dehydrogenase in the Mode of Action of the Redox-Active Antimalarial Drug, Plasmodione.” Free Radical Biology and Medicine 162 (January): 533–41. https://doi.org/10.1016/j.freeradbiomed.2020.11.010.
di Punzio, Giulia, Maria Antonietta Di Noia, Agnès Delahodde, Carole H. Sellem, Claudia Donnini, Luigi Palmieri , Tiziana Lodi, and Cristina Dallabona. 2021. “A Yeast-Based Screening Unravels Potential Therapeutic Molecules for Mitochondrial Diseases Associated with Dominant ANT1 Mutations” Int. J. Mol. Sci. 2021, 22, 4461. https://doi.org/10.3390/ijms22094461.
2020
Fisher, Nicholas, Brigitte Meunier, and Giancarlo A. Biagini. 2020. “The Cytochrome bc1 Complex as an Antipathogenic Target.” FEBS Letters 594 (18): 2935–52. https://doi.org/https://doi.org/10.1002/1873-3468.13868.
Wortmann, Saskia B., Brigitte Meunier, Lamia Mestek-Boukhibar, Florence van den Broek, Elaina M. Maldonado, Emma Clement, Daniel Weghuber, et al. 2020. “Bi-Allelic Variants in TKFC Encoding Triokinase/FMN Cyclase Are Associated with Cataracts and Multisystem Disease.” American Journal of Human Genetics 106 (2): 256–63. https://doi.org/10.1016/j.ajhg.2020.01.005.
Song, Zehua, Yangfeng Hu, Bogdan I. Iorga, Cindy Vallières, Nicholas Fisher, and Brigitte Meunier. 2020. “Mutational Analysis of the Qi-Site Proton Pathway in Yeast Cytochrome bc1 Complex.” Biochemical and Biophysical Research Communications 523 (3): 615–19. https://doi.org/10.1016/j.bbrc.2019.12.102.
Hartley, Andrew M., Brigitte Meunier, Nikos Pinotsis, and Amandine Maréchal. 2020. “Rcf2 Revealed in Cryo-EM Structures of Hypoxic Isoforms of Mature Mitochondrial III-IV Supercomplexes.” Proceedings of the National Academy of Sciences of the United States of America 117 (17): 9329–37. https://doi.org/10.1073/pnas.1920612117.
Maréchal, Amandine, Jing-Yang Xu, Naho Genko, Andrew M. Hartley, Francis Haraux, Brigitte Meunier, and Peter R. Rich. 2020. “A Common Coupling Mechanism for a-Type Heme-Copper Oxidases from Bacteria to Mitochondria.” Proceedings of the National Academy of Sciences of the United States of America 117 (17): 9349–55. https://doi.org/10.1073/pnas.2001572117.
Laleve, Anais, Cristina Panozzo, Inge Kühl, Alexa Bourand-Plantefol, Jelena Ostojic, Abdoulaye Sissoko, Déborah Tribouillard-Tanvier, David Cornu, Angélique Burg, Brigitte Meunier, Marc Blondel, Jérôme Clain, Nathalie Bonnefoy, Romain Duval, Geneviève Dujardin. 2020. “Artemisinin and Its Derivatives Target Mitochondrial c-Type Cytochromes in Yeast and Human Cells.” Biochimica Et Biophysica Acta. Molecular Cell Research 1867 (5): 118661. https://doi.org/10.1016/j.bbamcr.2020.118661.
Sellem, Carole H., Aurélie Renaud, Agnès Delahodde, and Vincent Procassio. 2020. “Use of Alverine or its derivative for the treatment of mitochondrial dideases or dysfunction associated with mitochondrial complex I deficiency”.
Brevet déposé le 20/07/2020 à l’European Patent Office 80298 Munich Germany
Patent N°20305857.3 – 1112
2019
Silva Ramos, Eduardo, Elisa Motori, Christian Brüser, Inge Kühl, Assa Yeroslaviz, Benedetta Ruzzenente, Johanna H. K. Kauppila, et al. 2019. “Mitochondrial Fusion Is Required for Regulation of Mitochondrial DNA Replication.” PLOS Genetics 15 (6): e1008085. https://doi.org/10.1371/journal.pgen.1008085.
Hartley, Andrew M., Natalya Lukoyanova, Yunyi Zhang, Alfredo Cabrera-Orefice, Susanne Arnold, Brigitte Meunier, Nikos Pinotsis, and Amandine Maréchal. 2019. “Structure of Yeast Cytochrome c Oxidase in a Supercomplex with Cytochrome bc1.” Nature Structural & Molecular Biology 26 (1): 78–83. https://doi.org/10.1038/s41594-018-0172-z.
Jiang, Shan, Camilla Koolmeister, Jelena Misic, Stefan Siira, Inge Kühl, Eduardo Silva Ramos, Maria Miranda, et al. 2019. “TEFM Regulates Both Transcription Elongation and RNA Processing in Mitochondria.” EMBO Reports 20 (6): e48101. https://doi.org/10.15252/embr.201948101.
Mounkoro, Pierre, Thomas Michel, Stéphanie Blandin, Marie-Pierre Golinelli-Cohen, Elisabeth Davioud-Charvet, and Brigitte Meunier. 2019. “Investigating the Mode of Action of the Redox-Active Antimalarial Drug Plasmodione Using the Yeast Model.” Free Radical Biology & Medicine 141 (June): 269–78. https://doi.org/10.1016/j.freeradbiomed.2019.06.026.
Keatley, Kathleen, Samuel Stromei-Cleroux, Tammy Wiltshire, Nina Rajala, Gary Burton, William V. Holt, D. Timothy J. Littlewood, et al. 2019. “Integrated Approach Reveals Role of Mitochondrial Germ-Line Mutation F18L in Respiratory Chain, Oxidative Alterations, Drug Sensitivity, and Patient Prognosis in Glioblastoma.” International Journal of Molecular Sciences 20 (13): 3364. https://doi.org/10.3390/ijms20133364.
Malkamäki, Aapo, Brigitte Meunier, Marco Reidelbach, Peter R. Rich, and Vivek Sharma. 2019. “The H Channel Is Not a Proton Transfer Path in Yeast Cytochrome c Oxidase.” Biochimica Et Biophysica Acta. Bioenergetics 1860 (9): 717–23. https://doi.org/10.1016/j.bbabio.2019.07.012.
Mounkoro, Pierre, Thomas Michel, Rafik Benhachemi, Georgiana Surpateanu, Bogdan I. Iorga, Nicholas Fisher, and Brigitte Meunier. 2019. “Mitochondrial Complex III Qi -Site Inhibitor Resistance Mutations Found in Laboratory Selected Mutants and Field Isolates.” Pest Management Science 75 (8): 2107–14. https://doi.org/10.1002/ps.5264.
Björck, Markus L., Jóhanna Vilhjálmsdóttir, Andrew M. Hartley, Brigitte Meunier, Linda Näsvik Öjemyr, Amandine Maréchal, and Peter Brzezinski. 2019. “Proton-Transfer Pathways in the Mitochondrial S. cerevisiae Cytochrome c Oxidase.” Scientific Reports 9 (1): 20207. https://doi.org/10.1038/s41598-019-56648-9.
Sellem, Carole H., Adeline Humbert, and Annie Sainsard-Chanet. 2019.
Mutations in the phosphatase domain of the 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase result in the transcriptional activation of the alternative oxidase and gluconeogenic pathways in Podospora anserina.
Fungal Genet Biol. 130 :1-10. https://doi.org/10.1016/j.fgb.2019.04.005
2018
Song, Zehua, Bogdan I. Iorga, Pierre Mounkoro, Nicholas Fisher, and Brigitte Meunier. 2018. “The Antimalarial Compound ELQ-400 Is an Unusual Inhibitor of the bc1 Complex, Targeting Both Qo and Qi Sites.” FEBS Letters 592 (8): 1346–56. https://doi.org/https://doi.org/10.1002/1873-3468.13035.
Naquin, Delphine, Cristina Panozzo, Genevieve Dujardin, Erwin van Dijk, Yves D’Aubenton-Carafa, and Claude Thermes. 2018. “Complete Sequence of the Intronless Mitochondrial Genome of the Saccharomyces cerevisiae Strain CW252.” Microbiology Resource Announcements 6 (17): UNSP e00219-18. https://doi.org/10.1128/genomeA.00219-18.
Dreinert, Adalbert, Antje Wolf, Tobias Mentzel, Brigitte Meunier, and Marcus Fehr. 2018. “The Cytochrome bc1 Complex Inhibitor Ametoctradin Has an Unusual Binding Mode.” Biochimica et Biophysica Acta (BBA) – Bioenergetics 1859 (8): 567–76. https://doi.org/10.1016/j.bbabio.2018.04.008.
Maréchal, Amandine, Andrew M. Hartley, Thomas P. Warelow, Brigitte Meunier, and Peter R. Rich. 2018. “Comparison of Redox and Ligand Binding Behaviour of Yeast and Bovine Cytochrome c Oxidases Using FTIR Spectroscopy.” Biochimica et Biophysica Acta (BBA) – Bioenergetics 1859 (9): 705–11. https://doi.org/10.1016/j.bbabio.2018.05.018.
2017
He, Cuiwen H., Dylan S. Black, Christopher M. Allan, Brigitte Meunier, Shamima Rahman, and Catherine F. Clarke. 2017. “Human COQ9 Rescues a Coq9 Yeast Mutant by Enhancing Coenzyme Q Biosynthesis from 4-Hydroxybenzoic Acid and Stabilizing the CoQ-Synthome.” Frontiers in Physiology 8: 463. https://doi.org/10.3389/fphys.2017.00463.
Khalimonchuk, Oleh, Megan Bestwick, Brigitte Meunier, Talina C. Watts, and Dennis R. Winge. 2017. “Correction for Khalimonchuk et al., ‘Formation of the Redox Cofactor Centers during Cox1 Maturation in Yeast Cytochrome Oxidase.’” Molecular and Cellular Biology 37 (11). https://doi.org/10.1128/MCB.00127-17.
Glatigny, Annie, Philippe Gambette, Alexa Bourand-Plantefol, Geneviève Dujardin, and Marie-Hélène Mucchielli-Giorgi. 2017. “Development of an in Silico Method for the Identification of Subcomplexes Involved in the Biogenesis of Multiprotein Complexes in Saccharomyces cerevisiae.” BMC Systems Biology 11 (1): 67. https://doi.org/10.1186/s12918-017-0442-0.
Kühl, Inge, Maria Miranda, Ilian Atanassov, Irina Kuznetsova, Yvonne Hinze, Arnaud Mourier, Aleksandra Filipovska, and Nils-Göran Larsson. 2017. “Transcriptomic and Proteomic Landscape of Mitochondrial Dysfunction Reveals Secondary Coenzyme Q Deficiency in Mammals.” ELife 6 (November): e30952. https://doi.org/10.7554/eLife.30952.
Panozzo, C., A. Laleve, D. Tribouillard-Tanvier, J. Ostojić, C. H. Sellem, G. Friocourt, A. Bourand-Plantefol, et al. 2017. “Chemicals or Mutations That Target Mitochondrial Translation Can Rescue the Respiratory Deficiency of Yeast bcs1 Mutants.” Biochimica et Biophysica Acta (BBA) – Molecular Cell Research 1864 (12): 2297–2307. https://doi.org/10.1016/j.bbamcr.2017.09.003.
2016
Lalève, Anaïs, Cindy Vallières, Marie-Pierre Golinelli-Cohen, Cécile Bouton, Zehua Song, Grzegorz Pawlik, Sarah M. Tindall, Simon V. Avery, Jérôme Clain, and Brigitte Meunier. 2016. “The Antimalarial Drug Primaquine Targets Fe–S Cluster Proteins and Yeast Respiratory Growth.” Redox Biology 7: 21–29. https://doi.org/10.1016/j.redox.2015.10.008.
Delerue, Thomas, Farnoosh Khosrobakhsh, Marlène Daloyau, Laurent Jean Emorine, Adrien Dedieu, Christopher J. Herbert, Nathalie Bonnefoy, Laetitia Arnauné-Pelloquin, and Pascale Belenguer. 2016. “Loss of Msp1p in Schizosaccharomyces pombe Induces a ROS-Dependent Nuclear Mutator Phenotype That Affects Mitochondrial Fission Genes.” FEBS Letters 590 (20): 3544–58. https://doi.org/10.1002/1873-3468.12432.
Ostojić, Jelena, Cristina Panozzo, Alexa Bourand-Plantefol, Christopher J. Herbert, Geneviève Dujardin, and Nathalie Bonnefoy. 2016. “Ribosome Recycling Defects Modify the Balance between the Synthesis and Assembly of Specific Subunits of the Oxidative Phosphorylation Complexes in Yeast Mitochondria.” Nucleic Acids Research 44 (12): 5785–97. https://doi.org/10.1093/nar/gkw490.
Song, Zehua, Anaïs Laleve, Cindy Vallières, John E. McGeehan, Rhiannon E. Lloyd, and Brigitte Meunier. 2016. “Human Mitochondrial Cytochrome b Variants Studied in Yeast: Not All Are Silent Polymorphisms.” Human Mutation 37 (9): 933–41. https://doi.org/10.1002/humu.23024.
2015
Song, Zehua, Jérôme Clain, Bogdan I. Iorga, Cindy Vallières, Anaïs Lalève, Nicholas Fisher, and Brigitte Meunier. 2015. “Interplay between the Hinge Region of Iron Sulphur Protein and the Qo Site in the bc1 Complex — Analysis of Plasmodium-like Mutations in the Yeast Enzyme.” Biochimica et Biophysica Acta (BBA) – Bioenergetics 1847 (12): 1487–94. https://doi.org/10.1016/j.bbabio.2015.08.005.
Lasserre, J.-P., A. Dautant, R. S. Aiyar, R. Kucharczyk, A. Glatigny, D. Tribouillard-Tanvier, J. Rytka, et al. 2015. “Yeast as a System for Modeling Mitochondrial Disease Mechanisms and Discovering Therapies.” Disease Models & Mechanisms 8 (6): 509–26. https://doi.org/10.1242/dmm.020438.
Nesti, C., M. C. Meschini, B. Meunier, M. Sacchini, S. Doccini, A. Romano, S. Petrillo, et al. 2015. “Additive Effect of Nuclear and Mitochondrial Mutations in a Patient with Mitochondrial Encephalomyopathy.” Human Molecular Genetics 24 (11): 3248–56. https://doi.org/10.1093/hmg/ddv078.
Song, Zehua, Jérôme Clain, Bogdan I. Iorga, Zhou Yi, Nicholas Fisher, and Brigitte Meunier. 2015. “Saccharomyces Cerevisiae-Based Mutational Analysis of the bc1 Complex Qo Site Residue 279 to Study the Trade-off between Atovaquone Resistance and Function.” Antimicrobial Agents and Chemotherapy 59 (7): 4053–58. https://doi.org/10.1128/AAC.00710-15.
Lloyd, R. E., K. Keatley, D. T. J. Littlewood, B. Meunier, W. V. Holt, Q. An, S. C. Higgins, et al. 2015. “Identification and Functional Prediction of Mitochondrial Complex III and IV Mutations Associated with Glioblastoma.” Neuro-Oncology 17 (7): 942–52. https://doi.org/10.1093/neuonc/nov020.
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https://www.i2bc.paris-saclay.fr/wp-content/plugins/zotpress/
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0pauci-%20or%20asymptomatic%20children%20hospitalised%20in%20Paris%20during%20the%20first%20wave%20for%20reasons%20other%20than%20COVID%20%28hospitalised%20children%20%28HOS%29%2C%20n%5Cu2009%3D%5Cu2009739%29%20plus%20children%20presenting%20with%20MIS%20%28n%5Cu2009%3D%5Cu200936%29.%20SARS-CoV-2%20antibodies%20directed%20against%20the%20nucleoprotein%20%28N%29%20and%20S1%20and%20S2%20domains%20of%20the%20spike%20%28S%29%20proteins%20were%20monitored%20by%20an%20in-house%20luciferase%20immunoprecipitation%20system%20assay.%20We%20randomly%20selected%2069%20SARS-CoV-2-seropositive%20patients%20%28including%2015%20with%20MIS%29%20and%20115%20matched%20SARS-CoV-2-seronegative%20patients%20%28controls%20%28CTL%29%29.%20We%20measured%20antibodies%20against%20SARS-CoV-2%20and%20HCoV%20as%20evidence%20for%20prior%20corresponding%20infections%20and%20assessed%20if%20SARS-CoV-2%20prevalence%20of%20infection%20and%20levels%20of%20antibody%20responses%20were%20shaped%20by%20prior%20seasonal%20coronavirus%20infections.ResultsPrevalence%20of%20HCoV%20infections%20were%20similar%20in%20HOS%2C%20MIS%20and%20CTL%20groups.%20Antibody%20levels%20against%20HCoV%20were%20not%20significantly%20different%20in%20the%20three%20groups%20and%20were%20not%20related%20to%20the%20level%20of%20SARS-CoV-2%20antibodies%20in%20the%20HOS%20and%20MIS%20groups.%20SARS-CoV-2%20antibody%20profiles%20were%20different%20between%20HOS%20and%20MIS%20children.ConclusionPrior%20infection%20by%20seasonal%20coronaviruses%2C%20as%20assessed%20by%20serology%2C%20does%20not%20interfere%20with%20SARS-CoV-2%20infection%20and%20related%20MIS%20in%20children.%22%2C%22date%22%3A%222021-04%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.2807%5C%2F1560-7917.ES.2021.26.13.2001782%22%2C%22ISSN%22%3A%221560-7917%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%5D%2C%22dateModified%22%3A%222025-03-14T13%3A57%3A15Z%22%7D%7D%2C%7B%22key%22%3A%22QI3IQHY8%22%2C%22library%22%3A%7B%22id%22%3A3888256%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Ibrahimi%20et%20al.%22%2C%22parsedDate%22%3A%222021%22%2C%22numChildren%22%3A2%7D%2C%22bib%22%3A%22%26lt%3Bdiv%20class%3D%26quot%3Bcsl-bib-body%26quot%3B%20style%3D%26quot%3Bline-height%3A%201.35%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%26quot%3B%26gt%3B%5Cn%20%20%26lt%3Bdiv%20class%3D%26quot%3Bcsl-entry%26quot%3B%26gt%3BIbrahimi%2C%20Nusa%26%23xEF%3Bbah%2C%20Agn%26%23xE8%3Bs%20Delaunay-Moisan%2C%20Catherine%20Hill%2C%20et%20al.%202021.%20%26%23x201C%3BScreening%20for%20SARS-CoV-2%20by%20RT-PCR%3A%20Saliva%20or%20Nasopharyngeal%20Swab%3F%20Rapid%20Review%20and%20Meta-Analysis.%26%23x201D%3B%20%26lt%3Bi%26gt%3BPloS%20One%26lt%3B%5C%2Fi%26gt%3B%2016%20%286%29%3A%20e0253007.%20%26lt%3Ba%20class%3D%26%23039%3Bzp-DOIURL%26%23039%3B%20href%3D%26%23039%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1371%5C%2Fjournal.pone.0253007%26%23039%3B%26gt%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1371%5C%2Fjournal.pone.0253007%26lt%3B%5C%2Fa%26gt%3B.%26lt%3B%5C%2Fdiv%26gt%3B%5Cn%26lt%3B%5C%2Fdiv%26gt%3B%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Screening%20for%20SARS-CoV-2%20by%20RT-PCR%3A%20Saliva%20or%20nasopharyngeal%20swab%3F%20Rapid%20review%20and%20meta-analysis%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Nusa%5Cu00efbah%22%2C%22lastName%22%3A%22Ibrahimi%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Agn%5Cu00e8s%22%2C%22lastName%22%3A%22Delaunay-Moisan%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Catherine%22%2C%22lastName%22%3A%22Hill%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Gw%5Cu00e9na%5Cu00ebl%22%2C%22lastName%22%3A%22Le%20Teuff%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jean-Fran%5Cu00e7ois%22%2C%22lastName%22%3A%22Rupprecht%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jean-Yves%22%2C%22lastName%22%3A%22Thuret%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Dan%22%2C%22lastName%22%3A%22Chaltiel%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Marie-Claude%22%2C%22lastName%22%3A%22Potier%22%7D%5D%2C%22abstractNote%22%3A%22BACKGROUND%3A%20Diagnosis%20of%20COVID-19%20in%20symptomatic%20patients%20and%20screening%20of%20populations%20for%20SARS-CoV-2%20infection%20require%20access%20to%20straightforward%2C%20low-cost%20and%20high-throughput%20testing.%20The%20recommended%20nasopharyngeal%20swab%20tests%20are%20limited%20by%20the%20need%20of%20trained%20professionals%20and%20specific%20consumables%20and%20this%20procedure%20is%20poorly%20accepted%20as%20a%20screening%20method%20In%20contrast%2C%20saliva%20sampling%20can%20be%20self-administered.%5CnMETHODS%3A%20In%20order%20to%20compare%20saliva%20and%20nasopharyngeal%5C%2Foropharyngeal%20samples%20for%20the%20detection%20of%20SARS-CoV-2%2C%20we%20designed%20a%20meta-analysis%20searching%20in%20PubMed%20up%20to%20December%2029th%2C%202020%20with%20the%20key%20wor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Almyre, Claire, Nolwenn Bounaix, François Godard, et al. 2025. “The Copper Ionophore Disulfiram Improves Mitochondrial Function in Various Yeast and Human Cellular Models of Mitochondrial Diseases.” Human Molecular Genetics, April 29, ddaf061. https://doi.org/10.1093/hmg/ddaf061.
Salama, Ehab A., Yehia Elgammal, Aruna Wijeratne, et al. 2024. “Lansoprazole Interferes with Fungal Respiration and Acts Synergistically with Amphotericin B against Multidrug-Resistant Candida Auris.” Emerging Microbes & Infections 13 (1): 2322649. https://doi.org/10.1080/22221751.2024.2322649.
Salama, Ehab A., Yehia Elgammal, Aruna Wijeratne, et al. 2024. “Response to the Letter to the Editor: Lansoprazole Interferes with Fungal Respiration and Acts Synergistically with Amphotericin B against Multidrug-Resistant Candida Auris.” Emerging Microbes & Infections, August 28, 2396869. https://doi.org/10.1080/22221751.2024.2396869.
Dinh, Nhu, and Nathalie Bonnefoy. 2024. “Schizosaccharomyces Pombe as a Fundamental Model for Research on Mitochondrial Gene Expression: Progress, Achievements and Outlooks.” IUBMB Life 76 (7): 397–419. https://doi.org/10.1002/iub.2801.
Tremblay-Laganière, Camille, Coralie Michaud, Raphaël Abourjaili-Bilodeau, et al. 2024. “Homozygous Variant in TKFC Abolishing Triokinase Activities Is Associated with Isolated Immunodeficiency.” Journal of Medical Genetics, May 2, jmg-2024-109853. https://doi.org/10.1136/jmg-2024-109853.
Iacobucci, Ilaria, Vittoria Monaco, Agnès Hovasse, et al. 2024. “Proteomic Profiling of Antimalarial Plasmodione Using 3-Benz(o)Ylmenadione Affinity-Based Probes.” Chembiochem: A European Journal of Chemical Biology, April 19, e202400187. https://doi.org/10.1002/cbic.202400187.
Trometer, Nathan, Jérémy Pecourneau, Liwen Feng, et al. 2024. “Synthesis and Anti-Chagas Activity Profile of a Redox-Active Lead 3-Benzylmenadione Revealed by High-Content Imaging.” ACS Infectious Diseases, ahead of print, April 12. https://doi.org/10.1021/acsinfecdis.4c00137.
L’Hôte, Valentin, Régis Courbeyrette, Guillaume Pinna, et al. 2021. “Ouabain and Chloroquine Trigger Senolysis of BRAF-V600E-Induced Senescent Cells by Targeting Autophagy.” Aging Cell, August 6, e13447. https://doi.org/10.1111/acel.13447.
Luo, Ruibang, Agnès Delaunay-Moisan, Kenneth Timmis, and Antoine Danchin. 2021. “SARS-CoV-2 Biology and Variants: Anticipation of Viral Evolution and What Needs to Be Done.” Environmental Microbiology 23 (5): 2339–63. https://doi.org/10.1111/1462-2920.15487.
Sermet-Gaudelus, Isabelle, Sarah Temmam, Christèle Huon, et al. 2021. “Prior Infection by Seasonal Coronaviruses, as Assessed by Serology, Does Not Prevent SARS-CoV-2 Infection and Disease in Children, France, April to June 2020.” Euro Surveillance: Bulletin Europeen Sur Les Maladies Transmissibles = European Communicable Disease Bulletin 26 (13): 2001782. https://doi.org/10.2807/1560-7917.ES.2021.26.13.2001782.
Ibrahimi, Nusaïbah, Agnès Delaunay-Moisan, Catherine Hill, et al. 2021. “Screening for SARS-CoV-2 by RT-PCR: Saliva or Nasopharyngeal Swab? Rapid Review and Meta-Analysis.” PloS One 16 (6): e0253007. https://doi.org/10.1371/journal.pone.0253007.
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Young, David H., and Brigitte Meunier. 2023. “Characterization of Mutants with Single and Combined Qi and Qo Site Mutations in Saccharomyces Cerevisiae Reveals Interactions between the Picolinamide Fungicide CAS-649 and Azoxystrobin.” Pesticide Biochemistry and Physiology 189 (January): 105313. https://doi.org/10.1016/j.pestbp.2022.105313.
Bonnefoy, Nathalie, and Claire Remacle. 2023. “Biolistic Transformation of Chlamydomonas Reinhardtii and Saccharomyces Cerevisiae Mitochondria.” Methods in Molecular Biology (Clifton, N.J.) 2615: 345–64. https://doi.org/10.1007/978-1-0716-2922-2_24.
Reiner, Andreas, and Inge Kühl. 2022. “Highlight: Young Research Groups in Germany – 4th Edition.” Biological Chemistry, ahead of print, June 28. https://doi.org/10.1515/hsz-2022-0207.
Miranda, Maria, Nina A. Bonekamp, and Inge Kühl. 2022. “Starting the Engine of the Powerhouse: Mitochondrial Transcription and Beyond.” Biological Chemistry, ahead of print, March 31. https://doi.org/10.1515/hsz-2021-0416.
Young, David H., Brigitte Meunier, and Nick X. Wang. 2022. “Interaction of Picolinamide Fungicide Primary Metabolites UK-2A and CAS-649 with the Cytochrome Bc1 Complex Qi Site: Mutation Effects and Modeling in Saccharomyces Cerevisiae.” Pest Management Science n/a (n/a). https://doi.org/10.1002/ps.6893.
Ribeiro, João M., María Jesús Costas, Alicia Cabezas, Brigitte Meunier, Alexandros Onoufriadis, and José Carlos Cameselle. 2022. “The TKFC Ala185Thr Variant, Reported as ‘Null’ for Fructose Metabolism, Is Fully Active as Triokinase.” FEBS Letters n/a (n/a). https://doi.org/10.1002/1873-3468.14309.
Herbert, Christopher J., Sylvie Labarre-Mariotte, David Cornu, et al. 2021. “Translational Activators and Mitoribosomal Isoforms Cooperate to Mediate mRNA-Specific Translation in Schizosaccharomyces Pombe Mitochondria.” Nucleic Acids Research, October 11, gkab789. https://doi.org/10.1093/nar/gkab789.
Yang, Yiqing, Tongke Tang, Xiaolu Li, et al. 2021. “Design, Synthesis, and Biological Evaluation of Multiple Targeting Antimalarials.” Acta Pharmaceutica Sinica. B 11 (9): 2900–2913. https://doi.org/10.1016/j.apsb.2021.05.008.
Fouché, Guillaume, Thomas Michel, Anaïs Lalève, et al. 2021. “Directed Evolution Predicts Cytochrome b G37V Target Site Modification as Probable Adaptive Mechanism towards the QiI Fungicide Fenpicoxamid in Zymoseptoria Tritici.” Environmental Microbiology, ahead of print, September 7. https://doi.org/10.1111/1462-2920.15760.
Punzio, Giulia di, Maria Antonietta Di Noia, Agnès Delahodde, et al. 2021. “A Yeast-Based Screening Unravels Potential Therapeutic Molecules for Mitochondrial Diseases Associated with Dominant ANT1 Mutations.” International Journal of Molecular Sciences 22 (9): 4461. https://doi.org/10.3390/ijms22094461.
Mounkoro, Pierre, Thomas Michel, and Brigitte Meunier. 2021. “Revisiting the Mode of Action of the Antimalarial Proguanil Using the Yeast Model.” Biochemical and Biophysical Research Communications 534 (January): 94–98. https://doi.org/10.1016/j.bbrc.2020.12.004.
Mounkoro, Pierre, Thomas Michel, Marie-Pierre Golinelli-Cohen, Stéphanie Blandin, Elisabeth Davioud-Charvet, and Brigitte Meunier. 2021. “A Role for the Succinate Dehydrogenase in the Mode of Action of the Redox-Active Antimalarial Drug, Plasmodione.” Free Radical Biology and Medicine 162 (January): 533–41. https://doi.org/10.1016/j.freeradbiomed.2020.11.010.
Reidelbach, Marco, Christoph Zimmer, Brigitte Meunier, Peter R. Rich, and Vivek Sharma. 2021. “Electron Transfer Coupled to Conformational Dynamics in Cell Respiration.” Frontiers in Molecular Biosciences 8: 711436. https://doi.org/10.3389/fmolb.2021.711436.
Laleve, Anais, Cristina Panozzo, Inge Kühl, et al. 2020. “Artemisinin and Its Derivatives Target Mitochondrial C-Type Cytochromes in Yeast and Human Cells.” Biochimica Et Biophysica Acta. Molecular Cell Research 1867 (5): 118661. https://doi.org/10.1016/j.bbamcr.2020.118661.
Maréchal, Amandine, Jing-Yang Xu, Naho Genko, et al. 2020. “A Common Coupling Mechanism for A-Type Heme-Copper Oxidases from Bacteria to Mitochondria.” Proceedings of the National Academy of Sciences of the United States of America 117 (17): 9349–55. https://doi.org/10.1073/pnas.2001572117.
Hartley, Andrew M., Brigitte Meunier, Nikos Pinotsis, and Amandine Maréchal. 2020. “Rcf2 Revealed in Cryo-EM Structures of Hypoxic Isoforms of Mature Mitochondrial III-IV Supercomplexes.” Proceedings of the National Academy of Sciences of the United States of America 117 (17): 9329–37. https://doi.org/10.1073/pnas.1920612117.
Song, Zehua, Yangfeng Hu, Bogdan I. Iorga, Cindy Vallières, Nicholas Fisher, and Brigitte Meunier. 2020. “Mutational Analysis of the Qi-Site Proton Pathway in Yeast Cytochrome Bc1 Complex.” Biochemical and Biophysical Research Communications 523 (3): 615–19. https://doi.org/10.1016/j.bbrc.2019.12.102.
Wortmann, Saskia B., Brigitte Meunier, Lamia Mestek-Boukhibar, et al. 2020. “Bi-Allelic Variants in TKFC Encoding Triokinase/FMN Cyclase Are Associated with Cataracts and Multisystem Disease.” American Journal of Human Genetics 106 (2): 256–63. https://doi.org/10.1016/j.ajhg.2020.01.005.
Fisher, Nicholas, Brigitte Meunier, and Giancarlo A. Biagini. 2020. “The Cytochrome Bc1 Complex as an Antipathogenic Target.” FEBS Letters 594 (18): 2935–52. https://doi.org/https://doi.org/10.1002/1873-3468.13868.
Björck, Markus L., Jóhanna Vilhjálmsdóttir, Andrew M. Hartley, et al. 2019. “Proton-Transfer Pathways in the Mitochondrial S. Cerevisiae Cytochrome c Oxidase.” Scientific Reports 9 (1): 20207. https://doi.org/10.1038/s41598-019-56648-9.
Sellem, Carole H., Adeline Humbert, and Annie Sainsard-Chanet. 2019. “Mutations in the Phosphatase Domain of the 6-Phosphofructo-2-Kinase/Fructose 2,6-Bisphosphatase Result in the Transcriptional Activation of the Alternative Oxidase and Gluconeogenic Pathways in Podospora Anserina.” Fungal Genetics and Biology 130 (September): 1–10. https://doi.org/10.1016/j.fgb.2019.04.005.
Mounkoro, Pierre, Thomas Michel, Rafik Benhachemi, et al. 2019. “Mitochondrial Complex III Qi -Site Inhibitor Resistance Mutations Found in Laboratory Selected Mutants and Field Isolates.” Pest Management Science 75 (8): 2107–14. https://doi.org/10.1002/ps.5264.
Malkamäki, Aapo, Brigitte Meunier, Marco Reidelbach, Peter R. Rich, and Vivek Sharma. 2019. “The H Channel Is Not a Proton Transfer Path in Yeast Cytochrome c Oxidase.” Biochimica Et Biophysica Acta. Bioenergetics 1860 (9): 717–23. https://doi.org/10.1016/j.bbabio.2019.07.012.
Keatley, Kathleen, Samuel Stromei-Cleroux, Tammy Wiltshire, et al. 2019. “Integrated Approach Reveals Role of Mitochondrial Germ-Line Mutation F18L in Respiratory Chain, Oxidative Alterations, Drug Sensitivity, and Patient Prognosis in Glioblastoma.” International Journal of Molecular Sciences 20 (13): 3364. https://doi.org/10.3390/ijms20133364.
Mounkoro, Pierre, Thomas Michel, Stéphanie Blandin, Marie-Pierre Golinelli-Cohen, Elisabeth Davioud-Charvet, and Brigitte Meunier. 2019. “Investigating the Mode of Action of the Redox-Active Antimalarial Drug Plasmodione Using the Yeast Model.” Free Radical Biology & Medicine 141 (June): 269–78. https://doi.org/10.1016/j.freeradbiomed.2019.06.026.
Jiang, Shan, Camilla Koolmeister, Jelena Misic, et al. 2019. “TEFM Regulates Both Transcription Elongation and RNA Processing in Mitochondria.” EMBO Reports 20 (6): e48101. https://doi.org/10.15252/embr.201948101.
Hartley, Andrew M., Natalya Lukoyanova, Yunyi Zhang, et al. 2019. “Structure of Yeast Cytochrome c Oxidase in a Supercomplex with Cytochrome Bc1.” Nature Structural & Molecular Biology 26 (1): 78–83. https://doi.org/10.1038/s41594-018-0172-z.
Silva Ramos, Eduardo, Elisa Motori, Christian Brüser, et al. 2019. “Mitochondrial Fusion Is Required for Regulation of Mitochondrial DNA Replication.” PLOS Genetics 15 (6): e1008085. https://doi.org/10.1371/journal.pgen.1008085.
Maréchal, Amandine, Andrew M. Hartley, Thomas P. Warelow, Brigitte Meunier, and Peter R. Rich. 2018. “Comparison of Redox and Ligand Binding Behaviour of Yeast and Bovine Cytochrome c Oxidases Using FTIR Spectroscopy.” Biochimica et Biophysica Acta (BBA) - Bioenergetics 1859 (9): 705–11. https://doi.org/10.1016/j.bbabio.2018.05.018.
Dreinert, Adalbert, Antje Wolf, Tobias Mentzel, Brigitte Meunier, and Marcus Fehr. 2018. “The Cytochrome Bc1 Complex Inhibitor Ametoctradin Has an Unusual Binding Mode.” Biochimica et Biophysica Acta (BBA) - Bioenergetics 1859 (8): 567–76. https://doi.org/10.1016/j.bbabio.2018.04.008.
Naquin, Delphine, Cristina Panozzo, Genevieve Dujardin, Erwin van Dijk, Yves D’Aubenton-Carafa, and Claude Thermes. 2018. “Complete Sequence of the Intronless Mitochondrial Genome of the Saccharomyces Cerevisiae Strain CW252.” Microbiology Resource Announcements 6 (17): UNSP e00219-18. https://doi.org/10.1128/genomeA.00219-18.
Song, Zehua, Bogdan I. Iorga, Pierre Mounkoro, Nicholas Fisher, and Brigitte Meunier. 2018. “The Antimalarial Compound ELQ-400 Is an Unusual Inhibitor of the Bc1 Complex, Targeting Both Qo and Qi Sites.” FEBS Letters 592 (8): 1346–56. https://doi.org/https://doi.org/10.1002/1873-3468.13035.
Panozzo, C., A. Laleve, D. Tribouillard-Tanvier, et al. 2017. “Chemicals or Mutations That Target Mitochondrial Translation Can Rescue the Respiratory Deficiency of Yeast Bcs1 Mutants.” Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1864 (12): 2297–307. https://doi.org/10.1016/j.bbamcr.2017.09.003.
Kühl, Inge, Maria Miranda, Ilian Atanassov, et al. 2017. “Transcriptomic and Proteomic Landscape of Mitochondrial Dysfunction Reveals Secondary Coenzyme Q Deficiency in Mammals.” eLife 6 (November): e30952. https://doi.org/10.7554/eLife.30952.
Glatigny, Annie, Philippe Gambette, Alexa Bourand-Plantefol, Geneviève Dujardin, and Marie-Hélène Mucchielli-Giorgi. 2017. “Development of an in Silico Method for the Identification of Subcomplexes Involved in the Biogenesis of Multiprotein Complexes in Saccharomyces Cerevisiae.” BMC Systems Biology 11 (1): 67. https://doi.org/10.1186/s12918-017-0442-0.
Khalimonchuk, Oleh, Megan Bestwick, Brigitte Meunier, Talina C. Watts, and Dennis R. Winge. 2017. “Correction for Khalimonchuk et al., ‘Formation of the Redox Cofactor Centers during Cox1 Maturation in Yeast Cytochrome Oxidase.’” Molecular and Cellular Biology 37 (11). https://doi.org/10.1128/MCB.00127-17.
He, Cuiwen H., Dylan S. Black, Christopher M. Allan, Brigitte Meunier, Shamima Rahman, and Catherine F. Clarke. 2017. “Human COQ9 Rescues a Coq9 Yeast Mutant by Enhancing Coenzyme Q Biosynthesis from 4-Hydroxybenzoic Acid and Stabilizing the CoQ-Synthome.” Frontiers in Physiology 8: 463. https://doi.org/10.3389/fphys.2017.00463.
Song, Zehua, Anaïs Laleve, Cindy Vallières, John E. McGeehan, Rhiannon E. Lloyd, and Brigitte Meunier. 2016. “Human Mitochondrial Cytochrome b Variants Studied in Yeast: Not All Are Silent Polymorphisms.” Human Mutation 37 (9): 933–41. https://doi.org/10.1002/humu.23024.
Ostojić, Jelena, Cristina Panozzo, Alexa Bourand-Plantefol, Christopher J. Herbert, Geneviève Dujardin, and Nathalie Bonnefoy. 2016. “Ribosome Recycling Defects Modify the Balance between the Synthesis and Assembly of Specific Subunits of the Oxidative Phosphorylation Complexes in Yeast Mitochondria.” Nucleic Acids Research 44 (12): 5785–97. https://doi.org/10.1093/nar/gkw490.
Delerue, Thomas, Farnoosh Khosrobakhsh, Marlène Daloyau, et al. 2016. “Loss of Msp1p in Schizosaccharomyces Pombe Induces a ROS-Dependent Nuclear Mutator Phenotype That Affects Mitochondrial Fission Genes.” FEBS Letters 590 (20): 3544–58. https://doi.org/10.1002/1873-3468.12432.
Lalève, Anaïs, Cindy Vallières, Marie-Pierre Golinelli-Cohen, et al. 2016. “The Antimalarial Drug Primaquine Targets Fe–S Cluster Proteins and Yeast Respiratory Growth.” Redox Biology 7: 21–29. https://doi.org/10.1016/j.redox.2015.10.008.
Lloyd, R. E., K. Keatley, D. T. J. Littlewood, et al. 2015. “Identification and Functional Prediction of Mitochondrial Complex III and IV Mutations Associated with Glioblastoma.” Neuro-Oncology 17 (7): 942–52. https://doi.org/10.1093/neuonc/nov020.
Song, Zehua, Jérôme Clain, Bogdan I. Iorga, Zhou Yi, Nicholas Fisher, and Brigitte Meunier. 2015. “Saccharomyces Cerevisiae-Based Mutational Analysis of the Bc1 Complex Qo Site Residue 279 to Study the Trade-off between Atovaquone Resistance and Function.” Antimicrobial Agents and Chemotherapy 59 (7): 4053–58. https://doi.org/10.1128/AAC.00710-15.
Nesti, C., M. C. Meschini, B. Meunier, et al. 2015. “Additive Effect of Nuclear and Mitochondrial Mutations in a Patient with Mitochondrial Encephalomyopathy.” Human Molecular Genetics 24 (11): 3248–56. https://doi.org/10.1093/hmg/ddv078.
Lasserre, J.-P., A. Dautant, R. S. Aiyar, et al. 2015. “Yeast as a System for Modeling Mitochondrial Disease Mechanisms and Discovering Therapies.” Disease Models & Mechanisms 8 (6): 509–26. https://doi.org/10.1242/dmm.020438.
Song, Zehua, Jérôme Clain, Bogdan I. Iorga, et al. 2015. “Interplay between the Hinge Region of Iron Sulphur Protein and the Qo Site in the Bc1 Complex — Analysis of Plasmodium-like Mutations in the Yeast Enzyme.” Biochimica et Biophysica Acta (BBA) - Bioenergetics 1847 (12): 1487–94. https://doi.org/10.1016/j.bbabio.2015.08.005.