Abstract
How inherent redox activity arises in biomolecular condensates remains unclear. Unlike interfacial systems, such as water microdroplets, where water oxidation underpins redox chemistry, condensates comprise biomolecules that can potentially furnish alternative electron-transfer routes. Here, using electron paramagnetic resonance, electrochemical potentiometry, mass spectrometry, and confocal microscopy assays, we discovered that orthogonal to water oxidation, microenvironment-dependent spontaneous tyrosine oxidation encodes an alternative redox pathway. Through proton-coupled electron transfer, self-induced tyrosine autoxidation in condensates drives the formation of reactive carbon and oxygen species, providing a pathway in parallel to hydroxide oxidation for hydrogen peroxide formation in condensates. This self-induced redox pathway modulates nonequilibrium condensate behaviors, including responses to external chemical perturbations and evolution of the condensate interior microenvironment. By correlating condensate biomolecular composition with inherent redox activities, our work establishes a conceptual framework suggesting that condensate-dependent electron transfer can be critical to define the functions of condensates and deliver a new redox mechanism for cell biology.