Bacterial respiration

In cellular respiration, reduction of a terminal electron acceptor is linked to the production of a transmembrane proton gradient, essential for the survival of the organism. The terminal electron acceptor oxygen is, in our own mitochondria, reduced by the proton-pumping enzyme cytochrome c oxidase, which belongs to the superfamily of heme-copper oxidases (HCuOs). This is a large and diverse superfamily that also has bacterial nitric oxide reductases (NOR) as a member. NORs form part of an anaerobic respiration pathway termed denitrification, where they reduce the toxic intermediate nitric oxide (NO) to nitrous oxide. NORs can also be used for detoxification of NO produced by human macrophages, and the C-type HCuOs are the only terminal oxidases present in some pathogens such as Helicobacter pylori. Thus, these enzymes can also be targeted for drug/antibiotics development. Our research aims at elucidating the structure-function relationship, assembly, cross-reactivity, energy conservation, proton transfer mechanisms and evolution of the nitric oxide and oxygen-reducing heme-copper oxidases.

We are also involved in a collaboration project on 'The obligate respiratory supercomplex of Actinobacteria' funded by the Knut and Alice Wallenberg foundation, where we study the structure and function of both the terminal oxygen-reducing paths in Mycobacterium smegmatis; the ComplexIII-IV supercomplex and the cyt. bd oxidases. Targeting the respiratory chain is very promising for the development of new anti-mycobacterial drugs. For more information, see:

https://kaw.wallenberg.org/forskning/grundforskning-om-cellers-energifabriker-kan-bidra-till-nya-lakemedel

Group members

Johanna Vilhjalmsdottir, Postdoc

Sofia Appelgren, PhD student

Mateusz Janczak, PhD student

Finja König, PhD student

Selected Publications

• Janczak, M., Vilhjalmsdottir, J., and Ädelroth, P. (2024) ‘Proton transfer in cytochrome bd-I from E. coli involves Asp-105 in CydB’, Biochim. Biophys. Acta 1865, 149489. https://doi.org/10.1016/j.bbabio.2024.149489
• di Trani, J. M., Gheorghita, A. A., Turner, M., Brzezinski, P., Ädelroth, P., Vahidi, S., Howell, P. L., Rubinstein, J. L. (2023) ‘Structure of the bc1-cbb3 respiratory supercomplex from Pseudomonas aeruginosa’, Proc. Natl. Acad. Sci., USA, 120, e2307093120. https://doi.org/10.1073/pnas.2307093120
• Kahle, M.*, Appelgren, S., Elofsson, A., Carroni, M*., Ädelroth, P*. (2023) ‘Insights into the structure-function relationship of the NorQ/NorD chaperones from Paracoccus denitrificans reveal shared principles of interacting MoxR AAA+/VWA domain proteins’, BMC Biol. 21, 47. https://doi.org/10.1186/s12915-023-01546-w
• Moe, A., Ädelroth, P., Brzeinski, P*, Öjemyr, L. (2023) ‘Cryo-EM structure and function of S. pombe complex IV with bound respiratory supercomplex factor’. Comm. Chem. 2023;6(1):32. doi: https://doi.org/10.1038/s42004-023-00827-3
• Król, S., Fedotovskaya, O., Högbom, M., Ädelroth, P.* and Brzezinski, P.* (2022) ‘Electron and proton transfer in the M. smegmatis III2IV2 supercomplex’ (2022) Biochim. Biophys. Acta- Bioenergetics, 1863, 148585. https://doi.org/10.1016/j.bbabio.2022.148585
• Fedotovskaya, O., Albertsson, I., Nordlund, G., Hong, S., Gennis, R. B., Brzezinski, P., Ädelroth, P. (2021) ‘Identification of a cytochrome bc1-aa3 supercomplex in Rhodobacter sphaeroides’ Biochim. Biophys. Acta- Bioenergetics, 1862, 148433.
• Zhou S, Pettersson, P, Huang, J, Brzezinski, P., Pomès, R., Mäler, L., Ädelroth, P. (2021) ‘NMR Structure and Dynamics Studies of Yeast Respiratory Supercomplex Factor 2’. Structure 29(3), 275-283.e4.
• Wiseman, B., Nitharwal, R. G., Fedotovskaya, O., Schäfer, J., Guo, H., Kuang, Q., Benlekbir, S., Sjöstrand, D., Ädelroth, P., Rubinstein, J. L., Brzezinski, P., Högbom, M. (2018) ‘Structure of a functional obligate respiratory supercomplex from Mycobacterium smegmatis’, Nat. Struct. Mol. Biol., 25, 1128-1136.
• Kahle, M., ter Beek, J., Hosler, J.P., Ädelroth, P. (2018) ‘The insertion of the non-heme FeB cofactor into nitric oxide reductase from P. denitrificans depends on NorQ and NorD accessory proteins’, Biochim. Biophys. Acta – Bioenergetics, 1859, 1051.
• Zhou, S., Pettersson, P., Huang, J., Sjöholm, J., Sjöstrand, D., Pomès, R., Högbom, M., Brzezinski, P., Mäler, L., and Ädelroth, P. (2018) ‘Proc. Natl. Acad. Sci. USA 115, p. 3048-3053.
• Gonska, N., Young, D., Yuki, R., Okamoto, T., Hisano, T., Antonyuk, S., Hasnain, S. S., Muramoto, K., Shiro, Y., Tosha, T., Ädelroth, P. (2018) ‘Characterization of the quinol-dependent nitric oxide reductase from the pathogen Neisseria meningitidis, an electrogenic enzyme’, Scientific Reports 8, 3637.
• Poiana, F., von Ballmoos, C., Gonska, N., Blomberg, M., Ädelroth, P., and Brzezinski, P. (2017) ‘Splitting of the O-O Bond at the heme-copper catalytic site of respiratory oxidases’, Science Adv., 3, :e170027.
• Bhagi-Damodaran, A., Kahle, M., Shi, Y., Zhang, Y., Ӓdelroth, P., and Lu, Y. (2017) ‘Insights into how heme reduction potential modulates enzymatic activities of a myoglobin-based functional oxidase’, Angew. Chem., Int. Ed., 56, 6622-6626.
• Ahn, Y. O., Mahinthichaichan, P., Lee, H. J., Ouyang, H., Kaluka, D., Yeh, S. Arjona, D., Rousseau, D. L., Tajkhorshid, E., Ädelroth, P. and Gennis, R. B. (2014) ‘Conformational coupling between the active site and residues within the KC-channel of the Vibrio cholerae cbb3-type oxygen reductase’, Proc. Natl. Acad. Sci. USA, 111, E4419-E4428. 
• ter Beek, J., Krause, N., Reimann, J., Lachmann, P., and Ädelroth, P. (2013) ‘The Nitric-Oxide reductase from Paracoccus denitrificans uses a single proton pathway’, J. Biol. Chem., 288, 30626-30635.

Funding Sources

Our studies are supported by grants from the Swedish Research Council (VR) and the Knut and Alice Wallenberg foundation.