How most living organisms couple their metabolism to respiration
Respiration lies at the heart of energy conversion in most living organisms. It relies on electron transfer chains located in the membrane, where small molecules called quinones act as electrochemical shuttles. Among the molecules fueling these respiratory chains, NADH plays a central role. Produced by many metabolic reactions, it must be reoxidized for the cell to continue functioning. This step is carried out by NADH dehydrogenases. Type II enzymes, or NDH-II, are widespread in the living world. They are generally described as simple flavoproteins capable of directly associating with the membrane to access quinones. However, this view does not account for their full diversity.
A study, published in Nature Communications by scientists from the IBS and the LCB, shows that, at least in certain bacterial lineages, this perspective must be broadened : access to quinones can rely on a specialized protein tube, capable of recreating a hydrophobic environment comparable to that of the membrane, similar to the lipid tunnels involved in lipid transfer between membranes in eukaryotes and some prokaryotes.
A new principle for the organization of respiratory chains
By combining comparative genomics, bacterial genetics, biochemistry, and cryo-electron microscopy, the scientists uncovered an unexpected organization of the NADH dehydrogenase Ndh in the soil bacterium Bacillus subtilis. This enzyme does not function alone : it assembles with a partner protein, YjlC, belonging to the HMP (Helical Membrane Plug-in) protein family. Both proteins are essential for respiratory activity. Together, they form a unique assembly : four YjlC subunits build a hydrophobic tube onto which four Ndh enzymes attach. These units then stack into fibers that can reach nearly 100 nm in length. Filled with lipids and quinones, this tube functions as an extension of the membrane. It provides the enzyme with organized access to the quinone pool, while reassigning the function of the enzyme’s carboxy-terminal domain : instead of anchoring directly into the bilayer, it serves here as an attachment point to the tube formed by YjlC. Evolutionary analyses indicate that this system is specific to Bacillales and likely results from the recruitment of an ancestral HMP module, initially associated with other respiratory enzymes. This discovery thus shifts the classical image of NDH-II, previously considered as isolated, monotopic enzymes, toward that of supramolecular respiratory modules.
The study expands the repertoire of architectures used by bacteria to organize their respiratory chains. It shows that the same structural principle, a hydrophobic tunnel connected to the membrane, can be reused by evolution to link different enzymes to the quinone pool. Beyond shedding light on bacterial energy metabolism, this work paves the way for identifying other unknown assemblies. It could also inspire new strategies for organizing or controlling enzymatic reactions in biotechnological contexts.
In summary, this study highlights an original strategy for organizing a bacterial NADH dehydrogenase around a lipid tunnel, at the heart of respiration and the energy adaptation of microorganisms.
A Bacillales-specific tubular scaffold essential for NADH dehydrogenase activity. Seduk F, Osman R, Garcia PS, Bizien-Jaglin L, Juyoux P, Kosta A, Sauvage S, Maté MJ, Pierrel F, Lebrun R, Schoehn G, Yamaryo-Botté Y, Botté CY, Nicolet Y, Cherrier MV, Walburger A, Magalon A. Nat Commun. 2026 Jun 18. doi : 10.1038/s41467-026-74385-2. Epub ahead of print. PMID : 42315832.
Contact : Mickaël Cherrier, IBS/Metalloproteins Group