Hydrogen peroxide (H₂O₂) acts as a signaling messenger by triggering the reversible oxidation of redox-regulated proteins. It remains unclear how proteins can be oxidized by signaling levels of H₂O₂ in the presence of peroxiredoxins, which are highly efficient peroxide scavengers. Here we show that the rapid formation of disulfide bonds in cytosolic proteins is enabled, rather than competed, by cytosolic 2-Cys peroxiredoxins. Under the conditions tested, the combined deletion or depletion of cytosolic peroxiredoxins broadly frustrated H₂O₂-dependent protein thiol oxidation, which is the exact opposite of what would be predicted based on the assumption that H₂O₂ oxidizes proteins directly. We find that peroxiredoxins enable rapid and sensitive protein thiol oxidation by relaying H₂O₂-derived oxidizing equivalents to other proteins. Although these findings do not rule out the existence of Prx-independent H₂O₂ signaling mechanisms, they suggest a broader role for peroxiredoxins as sensors and transmitters of H₂O₂ signals than hitherto recognized.

过氧化氢 (H ₂ O ₂ ) 通过触发氧化还原调节蛋白的可逆氧化作为信号信使。目前尚不清楚在过氧化物酶（一种高效的过氧化物清除剂）存在的情况下，如何通过 H ₂ O _{2信号水平来氧化蛋白质。}在这里，我们表明细胞溶质蛋白中二硫键的快速形成是由细胞溶质 2-Cys 过氧化还原蛋白实现的，而不是竞争性的。在所测试的条件下，细胞溶质过氧化物酶的联合缺失或消耗广泛抑制了 H ₂ O _{2依赖性蛋白质硫醇氧化，这与基于 H 2}的假设所预测的完全相反。O ₂直接氧化蛋白质。我们发现过氧化还原蛋白通过将 H ₂ O ₂衍生的氧化等价物传递给其他蛋白质来实现快速和敏感的蛋白质硫醇氧化。尽管这些发现不排除存在不依赖于 Prx 的 H ₂ O ₂信号传导机制，但它们表明过氧化物还蛋白作为 H ₂ O ₂信号的传感器和传递器的作用比迄今为止所认识到的更广泛。