{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T03:13:43Z","timestamp":1783653223021,"version":"3.55.0"},"reference-count":77,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:00:00Z","timestamp":1767916800000},"content-version":"vor","delay-in-days":30,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004063","name":"Knut och Alice Wallenbergs Stiftelse","doi-asserted-by":"publisher","award":["2019.0043"],"award-info":[{"award-number":["2019.0043"]}],"id":[{"id":"10.13039\/501100004063","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004063","name":"Knut och Alice Wallenbergs Stiftelse","doi-asserted-by":"publisher","award":["2023.0201"],"award-info":[{"award-number":["2023.0201"]}],"id":[{"id":"10.13039\/501100004063","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Foundation to Prevent Antimicrobial Resistance"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Aerobic organisms obtain energy by linking electron transfer from NADH to O\n                    <jats:sub>2<\/jats:sub>\n                    , through the respiratory chain, to transmembrane proton translocation. In mycobacteria the respiratory chain is branched; the membrane-bound electron carrier menaquinol (MQH\n                    <jats:sub>2<\/jats:sub>\n                    ) donates electrons either to the O\n                    <jats:sub>2<\/jats:sub>\n                    -reducing cytochrome\n                    <jats:italic>bd<\/jats:italic>\n                    or a supercomplex that is composed of a complex (C) III\n                    <jats:sub>2<\/jats:sub>\n                    dimer flanked by two CIVs. Here, we measured the dimethyl-naphthoquinone (DMNQH\n                    <jats:sub>2,<\/jats:sub>\n                    a menaquinol analogue) oxidation:O\n                    <jats:sub>2<\/jats:sub>\n                    reduction activities of the CIII\n                    <jats:sub>2<\/jats:sub>\n                    CIV\n                    <jats:sub>2<\/jats:sub>\n                    supercomplex and cytochrome\n                    <jats:italic>bd<\/jats:italic>\n                    in the presence of an analogue (decylubiquinone, DCQ) of the mammalian electron carrier, ubiquinol. The data show that DCQH\n                    <jats:sub>2<\/jats:sub>\n                    inhibits both the CIII\n                    <jats:sub>2<\/jats:sub>\n                    CIV\n                    <jats:sub>2<\/jats:sub>\n                    and cytochrome\n                    <jats:italic>bd<\/jats:italic>\n                    activities, suggesting that DCQ\/DCQH\n                    <jats:sub>2<\/jats:sub>\n                    interferes with both branches of the respiratory chain. Cryo-EM data of the\n                    <jats:italic>M. smegmatis<\/jats:italic>\n                    supercomplex shows that oxidized DCQ binds in the electron donor site (Q\n                    <jats:sub>o<\/jats:sub>\n                    ) of CIII\n                    <jats:sub>2<\/jats:sub>\n                    . Accordingly, growth of\n                    <jats:italic>M. smegmatis<\/jats:italic>\n                    cells was impaired in the presence of DCQ. Remarkably, DCQ also impairs intracellular growth of virulent\n                    <jats:italic>M. tuberculosis<\/jats:italic>\n                    cells in human primary macrophages suggesting that the compound could potentially be used as an adjuvant during tuberculosis disease treatment.\n                  <\/jats:p>","DOI":"10.1038\/s42003-025-09309-9","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T10:17:20Z","timestamp":1765361840000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Mycobacterial respiratory chain enzymes and growth are inhibited by decylubiquinone"],"prefix":"10.1038","volume":"9","author":[{"given":"Sylwia","family":"Kr\u00f3l","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0144-2463","authenticated-orcid":false,"given":"Terezia","family":"Kovalova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2291-8282","authenticated-orcid":false,"given":"Mateusz","family":"Janczak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadaf","family":"Kalsum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mira","family":"Akber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5574-9383","authenticated-orcid":false,"given":"Martin","family":"H\u00f6gbom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8540-153X","authenticated-orcid":false,"given":"Susanna","family":"Brighenti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0853-6785","authenticated-orcid":false,"given":"Pia","family":"\u00c4delroth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3860-4988","authenticated-orcid":false,"given":"Peter","family":"Brzezinski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,10]]},"reference":[{"key":"9309_CR1","doi-asserted-by":"publisher","first-page":"10244","DOI":"10.1021\/acs.chemrev.0c00249","volume":"120","author":"F Melin","year":"2020","unstructured":"Melin, F. & Hellwig, P. Redox properties of the membrane proteins from the respiratory chain. Chem. Rev. 120, 10244\u201310297 (2020).","journal-title":"Chem. Rev."},{"key":"9309_CR2","doi-asserted-by":"publisher","first-page":"9644","DOI":"10.1021\/acs.chemrev.1c00140","volume":"121","author":"P Brzezinski","year":"2021","unstructured":"Brzezinski, P., Moe, A. & \u00c4delroth, P. Structure and mechanism of respiratory III\u2013IV supercomplexes in bioenergetic membranes. Chem. Rev. 121, 9644\u20139673 (2021).","journal-title":"Chem. Rev."},{"key":"9309_CR3","doi-asserted-by":"publisher","first-page":"1804","DOI":"10.1021\/acs.chemrev.0c00830","volume":"121","author":"F Calisto","year":"2021","unstructured":"Calisto, F., Sousa, F. M., Sena, F. V., Refojo, P. N. & Pereira, M. M. Mechanisms of energy transduction by charge translocating membrane proteins. Chem. Rev. 121, 1804\u20131844 (2021).","journal-title":"Chem. Rev."},{"key":"9309_CR4","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1152\/physrev.00006.2014","volume":"95","author":"M Sarewicz","year":"2015","unstructured":"Sarewicz, M. & Osyczka, A. Electronic connection between the quinone and cytochrome c redox pools and its role in regulation of mitochondrial electron transport and redox signaling. Physiol. Rev. 95, 219\u2013243 (2015).","journal-title":"Physiol. Rev."},{"key":"9309_CR5","doi-asserted-by":"publisher","first-page":"2020","DOI":"10.1021\/acs.chemrev.0c00712","volume":"121","author":"M Sarewicz","year":"2021","unstructured":"Sarewicz, M. et al. Catalytic reactions and energy conservation in the cytochrome bc1 and b6f complexes of energy-transducing membranes. Chem. Rev. 121, 2020\u20132108 (2021).","journal-title":"Chem. Rev."},{"key":"9309_CR6","doi-asserted-by":"publisher","unstructured":"Di Trani, J. M. et al. Rieske head domain dynamics and indazole-derivative inhibition of Candida albicans complex III. Structure, https:\/\/doi.org\/10.1016\/j.str.2021.08.006 (2021).","DOI":"10.1016\/j.str.2021.08.006"},{"key":"9309_CR7","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1016\/j.molcel.2019.07.022","volume":"75","author":"JA Letts","year":"2019","unstructured":"Letts, J. A., Fiedorczuk, K., Degliesposti, G., Skehel, M. & Sazanov, L. A. Structures of rspiratory supercomplex I+III2 reveal functional and conformational crosstalk. Mol. Cell 75, 1131\u20131146.e1136 (2019).","journal-title":"Mol. Cell"},{"key":"9309_CR8","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1016\/j.str.2021.11.008","volume":"30","author":"A Moe","year":"2022","unstructured":"Moe, A. et al. The respiratory supercomplex from C. glutamicum. Structure 30, 338\u2013349.e333 (2022).","journal-title":"Structure"},{"key":"9309_CR9","doi-asserted-by":"publisher","unstructured":"Kao, W. C. et al. Structural basis for safe and efficient energy conversion in a respiratory supercomplex. Nat. Commun. 13, https:\/\/doi.org\/10.1038\/s41467-022-28179-x (2022).","DOI":"10.1038\/s41467-022-28179-x"},{"key":"9309_CR10","doi-asserted-by":"publisher","unstructured":"Yanofsky, D. J. et al. Structure of mycobacterial CIII2CIV2 respiratory supercomplex bound to the tuberculosis drug candidate telacebec (Q203). eLife 10, https:\/\/doi.org\/10.7554\/eLife.71959 (2021).","DOI":"10.7554\/eLife.71959"},{"key":"9309_CR11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1126\/science.aat8923","volume":"362","author":"H Gong","year":"2018","unstructured":"Gong, H. et al. An electron transfer path connects subunits of a mycobacterial respiratory supercomplex. Science 362, 1\u201311 (2018).","journal-title":"Science"},{"key":"9309_CR12","doi-asserted-by":"publisher","first-page":"1278","DOI":"10.1016\/j.bbabio.2012.11.008","volume":"1827","author":"D Xia","year":"2013","unstructured":"Xia, D. et al. Structural analysis of cytochrome bc1 complexes: implications to the mechanism of function. Biochim. Biophys. Acta 1827, 1278\u20131294 (2013).","journal-title":"Biochim. Biophys. Acta"},{"key":"9309_CR13","doi-asserted-by":"publisher","first-page":"2196","DOI":"10.1021\/cr500448t","volume":"115","author":"M Wikstr\u00f6m","year":"2015","unstructured":"Wikstr\u00f6m, M., Sharma, V., Kaila, V. R. I., Hosler, J. P. & Hummer, G. New perspectives on proton pumping in cellular respiration. Chem. Rev. 115, 2196\u20132221 (2015).","journal-title":"Chem. Rev."},{"key":"9309_CR14","doi-asserted-by":"publisher","first-page":"7062","DOI":"10.1021\/cr1002003","volume":"110","author":"VRI Kaila","year":"2010","unstructured":"Kaila, V. R. I., Verkhovsky, M. I. & Wikstr\u00f6m, M. Proton-coupled electron transfer in cytochrome oxidase. Chem. Rev. 110, 7062\u20137081 (2010).","journal-title":"Chem. Rev."},{"key":"9309_CR15","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1007\/s10863-008-9181-7","volume":"40","author":"P Brzezinski","year":"2008","unstructured":"Brzezinski, P. & Gennis, R. B. Cytochrome c oxidase: exciting progress and remaining mysteries. J. Bioenerg. Biomembr. 40, 521\u2013531 (2008).","journal-title":"J. Bioenerg. Biomembr."},{"key":"9309_CR16","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1016\/j.bbabio.2011.10.007","volume":"1817","author":"HJ Lee","year":"2012","unstructured":"Lee, H. J., Reimann, J., Huang, Y. & \u00c4delroth, P. Functional proton transfer pathways in the heme-copper oxidase superfamily. Biochim. Biophys. Acta 1817, 537\u2013544 (2012).","journal-title":"Biochim. Biophys. Acta"},{"key":"9309_CR17","doi-asserted-by":"publisher","first-page":"1705","DOI":"10.1016\/j.bbabio.2016.07.009","volume":"1857","author":"WC Kao","year":"2016","unstructured":"Kao, W. C. et al. The obligate respiratory supercomplex from Actinobacteria. Biochim. Biophys. Acta 1857, 1705\u20131714 (2016).","journal-title":"Biochim. Biophys. Acta"},{"key":"9309_CR18","doi-asserted-by":"publisher","first-page":"4339","DOI":"10.1074\/jbc.M210499200","volume":"278","author":"A Niebisch","year":"2003","unstructured":"Niebisch, A. & Bott, M. Purification of a cytochrome bc1-aa3 supercomplex with quinol oxidase activity from Corynebacterium glutamicum: identification of a fourth subunit of cytochrome aa3 oxidase and mutational analysis of diheme cytochrome c1. J. Biol. Chem. 278, 4339\u20134346 (2003).","journal-title":"J. Biol. Chem."},{"key":"9309_CR19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1128\/microbiolspec.MGM2-0015-2013","volume":"2","author":"GM Cook","year":"2014","unstructured":"Cook, G. M., Hards, K., Vilch\u00e8ze, C., Hartman, T. & Berney, M. Energetics of respiration and oxidative phosphorylation in mycobacteria. Microbiol. Spectr. 2, 1\u201323 (2014).","journal-title":"Microbiol. Spectr."},{"key":"9309_CR20","doi-asserted-by":"publisher","unstructured":"Cook, G. M. et al. Oxidative phosphorylation as a target space for tuberculosis: Success, caution, and future directions. Microbiol. Spectr. 5, https:\/\/doi.org\/10.1128\/microbiolspec.TBTB2-0014-2016 (2017).","DOI":"10.1128\/microbiolspec.TBTB2-0014-2016"},{"key":"9309_CR21","doi-asserted-by":"publisher","unstructured":"Friedrich, T., Wohlwend, D. & Borisov, V. B. Recent advances in structural studies of cytochrome bd and its potential application as a drug target. Int. J. Mol. Sci. 23, https:\/\/doi.org\/10.3390\/ijms23063166 (2022).","DOI":"10.3390\/ijms23063166"},{"key":"9309_CR22","doi-asserted-by":"publisher","unstructured":"Grund, T. N. et al. Mechanistic and structural diversity between cytochrome bd isoforms of Escherichia coli. Proc. Natl. Acad. Sci. USA. 118, https:\/\/doi.org\/10.1073\/pnas.2114013118 (2021).","DOI":"10.1073\/pnas.2114013118"},{"key":"9309_CR23","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1126\/science.aay0967","volume":"366","author":"S Safarian","year":"2019","unstructured":"Safarian, S. et al. Active site rearrangement and structural divergence in prokaryotic respiratory oxidases. Science 366, 100\u2013104 (2019).","journal-title":"Science"},{"key":"9309_CR24","doi-asserted-by":"publisher","unstructured":"Grauel, A. et al. Structure of Escherichia coli cytochrome bd-II type oxidase with bound aurachin D. Nat. Commun. 12, https:\/\/doi.org\/10.1038\/s41467-021-26835-2 (2021).","DOI":"10.1038\/s41467-021-26835-2"},{"key":"9309_CR25","doi-asserted-by":"publisher","unstructured":"Grund, T. N. et al. The cryoEM structure of cytochrome bd from C. glutamicum provides novel insights into structural properties of actinobacterial terminal oxidases. Front. Chem. 10, https:\/\/doi.org\/10.3389\/fchem.2022.1085463 (2023).","DOI":"10.3389\/fchem.2022.1085463"},{"key":"9309_CR26","doi-asserted-by":"publisher","unstructured":"Wang, W. et al. Cryo-EM structure of mycobacterial cytochrome bd reveals two oxygen access channels. Nat. Commun. 12, https:\/\/doi.org\/10.1038\/s41467-021-24924-w (2021).","DOI":"10.1038\/s41467-021-24924-w"},{"key":"9309_CR27","doi-asserted-by":"publisher","unstructured":"Safarian, S. et al. The cryo-EM structure of the bd oxidase from M. tuberculosis reveals a unique structural framework and enables rational drug design to combat TB. Nat. Commun. 12, https:\/\/doi.org\/10.1038\/s41467-021-25537-z (2021).","DOI":"10.1038\/s41467-021-25537-z"},{"key":"9309_CR28","doi-asserted-by":"publisher","unstructured":"Chauhan, P. et al. Response of Mycobacterium smegmatis to the cytochrome bcc inhibitor Q203. Int. J. Mol. Sci. 23, https:\/\/doi.org\/10.3390\/ijms231810331 (2022).","DOI":"10.3390\/ijms231810331"},{"key":"9309_CR29","doi-asserted-by":"publisher","first-page":"7076","DOI":"10.1128\/JB.183.24.7076-7086.2001","volume":"183","author":"BD Kana","year":"2001","unstructured":"Kana, B. D. et al. Characterization of the cydAB-encoded cytochrome bd oxidase from Mycobacterium smegmatis. J. Bacteriol. 183, 7076\u20137086 (2001).","journal-title":"J. Bacteriol."},{"key":"9309_CR30","doi-asserted-by":"publisher","unstructured":"The\u00dfeling, A. et al. Homologous bd oxidases share the same architecture but differ in mechanism. Nat. Commun. 10, https:\/\/doi.org\/10.1038\/s41467-019-13122-4 (2019).","DOI":"10.1038\/s41467-019-13122-4"},{"key":"9309_CR31","doi-asserted-by":"publisher","first-page":"8549","DOI":"10.1073\/pnas.0813173106","volume":"106","author":"B Schoepp-Cothenet","year":"2009","unstructured":"Schoepp-Cothenet, B. et al. Menaquinone as pool quinone in a purple bacterium. Proc. Natl. Acad. Sci. USA 106, 8549\u20138554 (2009).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"9309_CR32","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/0014-5793(76)80821-6","volume":"72","author":"R Holl\u00e4nder","year":"1976","unstructured":"Holl\u00e4nder, R. Correlation of the function of demethylmenaquinone in bacterial electron transport with its redox potential. FEBS Lett. 72, 98\u2013100 (1976).","journal-title":"FEBS Lett."},{"key":"9309_CR33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/0005-2728(79)90166-X","volume":"546","author":"KI Takamiya","year":"1979","unstructured":"Takamiya, K. I. & Dutton, P. L. Ubiquinone in Rhodopseudomonas sphaeroides. Some thermodynamic properties. Biochim. Biophys. Acta 546, 1\u201316 (1979).","journal-title":"Biochim. Biophys. Acta"},{"key":"9309_CR34","doi-asserted-by":"crossref","unstructured":"Meganathan, R. Biosynthesis of menaquinone (vitamin K2) and ubiquinone (coenzyme Q): a perspective on enzymatic mechanisms. Vitam. Horm. 61, 173\u2013218 (2001).","DOI":"10.1016\/S0083-6729(01)61006-9"},{"key":"9309_CR35","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1016\/j.molcel.2015.10.016","volume":"60","author":"A Anand","year":"2015","unstructured":"Anand, A. et al. Polyketide quinones are alternate intermediate electron carriers during mycobacterial respiration in oxygen-deficient niches. Mol. Cell 60, 637\u2013650 (2015).","journal-title":"Mol. Cell"},{"key":"9309_CR36","doi-asserted-by":"publisher","first-page":"e8614","DOI":"10.1371\/journal.pone.0008614","volume":"5","author":"M Berney","year":"2010","unstructured":"Berney, M. & Cook, G. M. Unique flexibility in energy metabolism allows mycobacteria to combat starvation and hypoxia. PLoS ONE 5, e8614 (2010).","journal-title":"PLoS ONE"},{"key":"9309_CR37","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2023.105483","volume":"300","author":"SA Harden","year":"2024","unstructured":"Harden, S. A., Courbon, G. M., Liang, Y., Kim, A. S. & Rubinstein, J. L. A simple assay for inhibitors of mycobacterial oxidative phosphorylation. J. Biol. Chem. 300, 105483 (2024).","journal-title":"J. Biol. Chem."},{"key":"9309_CR38","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1126\/science.1106753","volume":"307","author":"K Andries","year":"2005","unstructured":"Andries, K. et al. A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis. Science 307, 223\u2013227 (2005).","journal-title":"Science"},{"key":"9309_CR39","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1038\/s41586-020-3004-3","volume":"589","author":"H Guo","year":"2021","unstructured":"Guo, H. et al. Structure of mycobacterial ATP synthase bound to the tuberculosis drug bedaquiline. Nature 589, 143\u2013147 (2021).","journal-title":"Nature"},{"key":"9309_CR40","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1038\/nm.3262","volume":"19","author":"K Pethe","year":"2013","unstructured":"Pethe, K. et al. Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis. Nat. Med. 19, 1157\u20131160 (2013).","journal-title":"Nat. Med."},{"key":"9309_CR41","doi-asserted-by":"publisher","unstructured":"Rybniker, J. et al. Lansoprazole is an antituberculous prodrug targeting cytochrome bc 1. Nat. Commun. 6, https:\/\/doi.org\/10.1038\/ncomms8659 (2015).","DOI":"10.1038\/ncomms8659"},{"key":"9309_CR42","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2412780121","volume":"121","author":"T Kovalova","year":"2024","unstructured":"Kovalova, T. et al. Inhibition mechanism of potential antituberculosis compound lansoprazole sulfide. Proc. Natl. Acad. Sci. USA 121, e2412780121 (2024).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"9309_CR43","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12956-2","volume":"10","author":"T Beites","year":"2019","unstructured":"Beites, T. et al. Plasticity of the Mycobacterium tuberculosis respiratory chain and its impact on tuberculosis drug development. Nat. Commun. 10, 4970 (2019).","journal-title":"Nat. Commun."},{"key":"9309_CR44","doi-asserted-by":"publisher","unstructured":"Berube Bryan, J. & Parish, T. Combinations of respiratory chain inhibitors have enhanced bactericidal activity against Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 62, https:\/\/doi.org\/10.1128\/aac.01677-01617, (2017).","DOI":"10.1128\/aac.01677-01617"},{"key":"9309_CR45","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1107\/S2052252522010570","volume":"10","author":"JP Wieferig","year":"2023","unstructured":"Wieferig, J. P., K\u00fchlbrandt, W. & Raunser, S. Analysis of the conformational heterogeneity of the Rieske iron-sulfur protein in complex III2 by cryo-EM. IUCrJ 10, 27\u201337 (2023).","journal-title":"IUCrJ"},{"key":"9309_CR46","doi-asserted-by":"publisher","first-page":"2346","DOI":"10.1016\/j.bmc.2013.01.075","volume":"21","author":"DM Fash","year":"2013","unstructured":"Fash, D. M. et al. Effects of alkyl side chain modification of coenzyme Q10 on mitochondrial respiratory chain function and cytoprotection. Bioorg. Med. Chem. 21, 2346\u20132354 (2013).","journal-title":"Bioorg. Med. Chem."},{"key":"9309_CR47","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-79136-1","volume":"14","author":"S Kalsum","year":"2024","unstructured":"Kalsum, S. et al. Sirtuin inhibitors reduce intracellular growth of M. tuberculosis in human macrophages via modulation of host cell immunity. Sci. Rep. 14, 28150 (2024).","journal-title":"Sci. Rep."},{"key":"9309_CR48","doi-asserted-by":"publisher","first-page":"1128","DOI":"10.1038\/s41594-018-0160-3","volume":"25","author":"B Wiseman","year":"2018","unstructured":"Wiseman, B. et al. Structure of a functional obligate complex III2IV2 respiratory supercomplex from Mycobacterium smegmatis. Nat. Struct. Mol. Biol. 25, 1128\u20131136 (2018).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"9309_CR49","doi-asserted-by":"publisher","unstructured":"Riepl, D. et al. Long-range charge transfer mechanism of the III2IV2 mycobacterial supercomplex. Nat. Commun. 15, https:\/\/doi.org\/10.1038\/s41467-024-49628-9 (2024).","DOI":"10.1038\/s41467-024-49628-9"},{"key":"9309_CR50","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1111\/j.1365-2958.2009.06625.x","volume":"72","author":"RK Dhiman","year":"2009","unstructured":"Dhiman, R. K. et al. Menaquinone synthesis is critical for maintaining mycobacterial viability during exponential growth and recovery from non-replicating persistence. Mol. Microbiol. 72, 85\u201397 (2009).","journal-title":"Mol. Microbiol."},{"key":"9309_CR51","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1042\/bj2530287","volume":"253","author":"PM Wood","year":"1988","unstructured":"Wood, P. M. The potential diagram for oxygen at pH 7. Biochem. J. 253, 287\u2013289 (1988).","journal-title":"Biochem. J."},{"key":"9309_CR52","doi-asserted-by":"publisher","unstructured":"van der Velden, T. T., Kayastha, K., Waterham, C. Y. J., Br\u00fcnle, S. & Jeuken, L. J. C. Menaquinone-specific turnover by Mycobacterium tuberculosis cytochrome bd is redox regulated by the Q-loop disulfide bond. J. Biol. Chem. 301, https:\/\/doi.org\/10.1016\/j.jbc.2024.108094 (2025).","DOI":"10.1016\/j.jbc.2024.108094"},{"key":"9309_CR53","doi-asserted-by":"publisher","first-page":"6962","DOI":"10.1128\/AAC.03486-14","volume":"58","author":"K Arora","year":"2014","unstructured":"Arora, K. et al. Respiratory flexibility in response to inhibition of cytochrome c oxidase in Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 58, 6962\u20136965 (2014).","journal-title":"Antimicrob. Agents Chemother."},{"key":"9309_CR54","doi-asserted-by":"publisher","first-page":"7426","DOI":"10.1073\/pnas.1706139114","volume":"114","author":"NP Kalia","year":"2017","unstructured":"Kalia, N. P. et al. Exploiting the synthetic lethality between terminal respiratory oxidases to kill Mycobacterium tuberculosis and clear host infection. Proc. Natl. Acad. Sci. USA 114, 7426\u20137431 (2017).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"9309_CR55","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202013207","volume":"13","author":"BS Lee","year":"2021","unstructured":"Lee, B. S. et al. Dual inhibition of the terminal oxidases eradicates antibiotic-tolerant Mycobacterium tuberculosis. EMBO Mol. Med. 13, e13207 (2021).","journal-title":"EMBO Mol. Med."},{"key":"9309_CR56","doi-asserted-by":"publisher","first-page":"5824","DOI":"10.3390\/molecules27185824","volume":"27","author":"R Vande Voorde","year":"2022","unstructured":"Vande Voorde, R., Dzalamidze, E., Nelson, D. & Danelishvili, L. Identification of small molecule inhibitors against Mycobacteria in activated macrophages. Molecules 27, 5824 (2022).","journal-title":"Molecules"},{"key":"9309_CR57","doi-asserted-by":"publisher","first-page":"6300","DOI":"10.1128\/JB.187.18.6300-6308.2005","volume":"187","author":"LG Matsoso","year":"2005","unstructured":"Matsoso, L. G. et al. Function of the cytochrome bc1-aa3 branch of the respiratory network in mycobacteria and network adaptation occurring in response to its disruption. J. Bacteriol. 187, 6300\u20136308 (2005).","journal-title":"J. Bacteriol."},{"key":"9309_CR58","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1038\/193702a0","volume":"193","author":"JO Norman","year":"1962","unstructured":"Norman, J. O. & Williams, R. P. Growth stimulation of Mycobacterium tuberculosis H37Rv by Coenzyme Q10. Nature 193, 702\u2013703 (1962).","journal-title":"Nature"},{"key":"9309_CR59","doi-asserted-by":"crossref","unstructured":"Liang, Y. et al. Coenzyme Q10 modulates the immunity by enhancing mononuclear macrophage, NK cell activity, and regulating gut microbiota. Front. Nutr. 12, 1504831 (2025).","DOI":"10.3389\/fnut.2025.1504831"},{"key":"9309_CR60","doi-asserted-by":"publisher","first-page":"759","DOI":"10.3390\/antiox10050759","volume":"10","author":"D Mantle","year":"2021","unstructured":"Mantle, D., Heaton, R. A. & Hargreaves, I. P. Coenzyme Q10 and immune function: an overview. Antioxidants 10, 759 (2021).","journal-title":"Antioxidants"},{"key":"9309_CR61","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.mito.2017.01.004","volume":"36","author":"P Yu-Wai-Man","year":"2017","unstructured":"Yu-Wai-Man, P., Soiferman, D., Moore, D. G., Burt\u00e9, F. & Saada, A. Evaluating the therapeutic potential of idebenone and related quinone analogues in Leber hereditary optic neuropathy. Mitochondrion 36, 36\u201342 (2017).","journal-title":"Mitochondrion"},{"key":"9309_CR62","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1007\/s10456-020-09707-z","volume":"23","author":"J Cao","year":"2020","unstructured":"Cao, J. et al. Decylubiquinone suppresses breast cancer growth and metastasis by inhibiting angiogenesis via the ROS\/p53\/ BAI1 signaling pathway. Angiogenesis 23, 325\u2013338 (2020).","journal-title":"Angiogenesis"},{"key":"9309_CR63","doi-asserted-by":"publisher","unstructured":"Kelly, A. G. & Panigrahy, D. Targeting Angiogenesis via Resolution of Inflammation. Cold Spring Harb. Perspect. Med. 13, https:\/\/doi.org\/10.1101\/cshperspect.a041172 (2023).","DOI":"10.1101\/cshperspect.a041172"},{"key":"9309_CR64","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-84852-z","volume":"11","author":"T Dadali","year":"2021","unstructured":"Dadali, T. et al. Elevated levels of mitochondrial CoQ(10) induce ROS-mediated apoptosis in pancreatic cancer. Sci. Rep. 11, 5749 (2021).","journal-title":"Sci. Rep."},{"key":"9309_CR65","doi-asserted-by":"publisher","first-page":"236","DOI":"10.3390\/antiox10020236","volume":"10","author":"JM Su\u00e1rez-Rivero","year":"2021","unstructured":"Su\u00e1rez-Rivero, J. M. et al. Coenzyme Q10 analogues: benefits and challenges for therapeutics. Antioxidants 10, 236 (2021).","journal-title":"Antioxidants"},{"key":"9309_CR66","doi-asserted-by":"crossref","unstructured":"Hasenoehrl, E. J., Wiggins, T. J. & Berney, M. Bioenergetic inhibitors: antibiotic efficacy and mechanisms of action in Mycobacterium tuberculosis. Front. Cell. Infect. Microbiol. 10, 611683 (2021).","DOI":"10.3389\/fcimb.2020.611683"},{"key":"9309_CR67","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1002\/biof.5520320121","volume":"32","author":"C Schmelzer","year":"2008","unstructured":"Schmelzer, C. et al. Functions of coenzyme Q10 in inflammation and gene expression. BioFactors 32, 179\u2013183 (2008).","journal-title":"BioFactors"},{"key":"9309_CR68","doi-asserted-by":"publisher","first-page":"103","DOI":"10.3109\/08923973.2015.1122619","volume":"38","author":"J Jhun","year":"2016","unstructured":"Jhun, J. et al. Combination therapy with metformin and coenzyme Q10 in murine experimental autoimmune arthritis. Immunopharmacol. Immunotoxicol. 38, 103\u2013112 (2016).","journal-title":"Immunopharmacol. Immunotoxicol."},{"key":"9309_CR69","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2023.111579","volume":"255","author":"JN Nyariki","year":"2023","unstructured":"Nyariki, J. N., Kimani, N. M., Kibet, P. S., Kinuthia, G. K. & Isaac, A. O. Coenzyme Q10 exhibits anti-inflammatory and immune-modulatory thereby decelerating the occurrence of experimental cerebral malaria. Mol. Biochem. Parasitol. 255, 111579 (2023).","journal-title":"Mol. Biochem. Parasitol."},{"key":"9309_CR70","doi-asserted-by":"publisher","first-page":"2606","DOI":"10.1089\/ars.2013.5406","volume":"20","author":"G Tian","year":"2013","unstructured":"Tian, G. et al. Ubiquinol-10 supplementation activates mitochondria functions to decelerate senescence in senescence-accelerated mice. Antioxid. Redox Signal. 20, 2606\u20132620 (2013).","journal-title":"Antioxid. Redox Signal."},{"key":"9309_CR71","doi-asserted-by":"publisher","first-page":"1923","DOI":"10.3390\/jcm9061923","volume":"9","author":"RA Heaton","year":"2020","unstructured":"Heaton, R. A., Heales, S., Rahman, K., Sexton, D. W. & Hargreaves, I. The effect of cellular coenzyme Q10 deficiency on lysosomal acidification. J. Clin. Med. 9, 1923 (2020).","journal-title":"J. Clin. Med."},{"key":"9309_CR72","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1111\/j.1744-313X.2011.01012.x","volume":"38","author":"W Cheng","year":"2011","unstructured":"Cheng, W. et al. Coenzyme Q plays opposing roles on bacteria\/fungi and viruses in Drosophila innate immunity. Int. J. Immunogenet. 38, 331\u2013337 (2011).","journal-title":"Int. J. Immunogenet."},{"key":"9309_CR73","doi-asserted-by":"publisher","first-page":"844","DOI":"10.2105\/AJPH.48.7.844","volume":"48","author":"G Middlebrook","year":"1958","unstructured":"Middlebrook, G. & Cohn, M. L. Bacteriology of Tuberculosis: laboratory methods. Am. J. Public Health Nations Health 48, 844\u2013853 (1958).","journal-title":"Am. J. Public Health Nations Health"},{"key":"9309_CR74","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1038\/nmeth.4169","volume":"14","author":"A Punjani","year":"2017","unstructured":"Punjani, A., Rubinstein, J. L., Fleet, D. J. & Brubaker, M. A. CryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination. Nat. Methods 14, 290\u2013296 (2017).","journal-title":"Nat. Methods"},{"key":"9309_CR75","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1107\/S0907444910007493","volume":"66","author":"P Emsley","year":"2010","unstructured":"Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. Sect. D Biol. Crystallogr. 66, 486\u2013501 (2010).","journal-title":"Acta Crystallogr. Sect. D Biol. Crystallogr."},{"key":"9309_CR76","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1107\/S0907444909052925","volume":"66","author":"PD Adams","year":"2010","unstructured":"Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. Sect. D Biol. Crystallogr. 66, 213\u2013221 (2010).","journal-title":"Acta Crystallogr. Sect. D Biol. Crystallogr."},{"key":"9309_CR77","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-24924-w","volume":"12","author":"W Wang","year":"2021","unstructured":"Wang, W. et al. Cryo-EM structure of mycobacterial cytochrome bd reveals two oxygen access channels. Nat. Commun. 12, 4621 (2021).","journal-title":"Nat. Commun."}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-09309-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-09309-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-09309-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T14:02:56Z","timestamp":1767967376000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-09309-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,10]]},"references-count":77,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["9309"],"URL":"https:\/\/doi.org\/10.1038\/s42003-025-09309-9","relation":{},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,10]]},"assertion":[{"value":"2 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 November 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"43"}}