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Optimal resource allocation is crucial to bacterial physiology and necessitates strategic metabolic decisions. One such evolutionary adaptation was the shift to high-potential respiratory chains following Earth’s Great Oxidation Event. Respiratory quinones, key redox-active electron carrier molecules, evolved from naphthoquinones (NQs) to ubiquinones (UQs) in response to oxygen availability. The two quinone types differ in their redox potential, with UQs possessing higher potential. Therefore, NQs are more autooxidizable and electron-leaky than UQs. Using adaptive laboratory evolution of a NQ-dependent Escherichia coli strain, we previously showed the fitness advantage of high-potential quinones. Here, we resolve a paradoxical growth benefit conferred by the loss of function of the pyruvate dehydrogenase complex regulator, revealing that NQs preferentially pair with the non-proton-pumping NADH dehydrogenase, thereby optimizing electron transport in low-potential respiratory chains under aerobic conditions.