Aerobic electrical ATP synthesis at mild redox potentials

Combining electrochemical and biochemical energy conversion approaches offers exciting opportunities for sustainable biotechnological applications. Here, we present an electrochemical system that directly powers oxidative phosphorylation under aerobic conditions at a mild redox potential of -0.16 V vs Ag/AgCl (0.05 V vs. SHE) by delivering electrons to a minimal respiratory chain reconstituted in liposomes. Using phenazine methosulfate (PMS) or its derivative as redox mediators, electrons are transferred across lipid membranes to cytochrome c, subsequently driving cytochrome aa₃ oxidase activity and ATP synthesis via F₁F_O ATP synthase. Furthermore, we extend this approach to native sub-mitochondrial particles (SMPs) extracted from bovine heart, demonstrating that such electrochemical reduction can also energise complex, natural respiratory machinery and support ATP production. This work establishes a novel strategy towards coupling electrical inputs to both minimal and native oxidative phosphorylation systems, paving the way for scalable biohybrid energy conversion technologies.