Isoprenoid quinones are molecules that have a major role in bioenergetics as they shuttle electrons across the respiratory chains of most living organisms. There are different quinone types that can be discriminated by their mid-point redox potential. This potential determines with which respiratory enzymes the quinones function, the respiratory substrates that are accessible, and ultimately the environment in which the organisms can live. In Proteobacteria, the two main quinones are menaquinone (MK), a low potenial quinone (~-80 mV) and ubiquinone (UQ), a high potential one (~+100 mV). So far, UQ was considered well adapted for the respiration of dioxygen, while MK would rather be involved in anaerobic respiration in O2-deprived contexts. However, our team recently discovered an O2-independent biosynthetic pathway for UQ production, while the classical pathway depends on the presence of O2 [1]. It was shown that this O2-independent pathway is crucial for anaerobic respiration (denitrification) in Pseudomonas aeruginosa [2]. Thus, these discoveries challenge the respective assumed physiological roles and origins of the MK and UQ pathways in Proteobacteria. In this study, we systematically investigated the quinone production potential across Proteobacteria through the annotation of quinone (MK and UQ) biosynthetic pathways in a large set of complete genomes. Particular attention was paid to the genes specific of the UQ O2-independent pathway (ubiT, -U and -V) for which we started to reconstitute the evolutionary history. We also addressed the question of their genetic architecture and regulation. Altogether, this large-scale study gives us more insights while inviting us to revisit the classical view of the respective physiological roles of the respiratory quinones found in Proteobacteria. [1] Pelosi L, Vo C-D-T, Abby SS, Loiseau L, Rascalou B, Chehade MH, Faivre B, Goussé M, Chenal C, Touati N, et al (2019) Ubiquinone Biosynthesis over the Entire O2 Range: Characterization of a Conserved O2-Independent Pathway. 10: 21 [2] Vo C-D-T, Michaud J, Elsen S, Faivre B, Bouveret E, Barras F, Fontecave M, Pierrel F, Lombard M & Pelosi L (2020) The O2-independent pathway of ubiquinone biosynthesis is essential for denitrification in Pseudomonas aeruginosa. Journal of Biological Chemistry 295: 9021-9032