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Hydrogen molecule (H2) exhibits broad-spectrum but microenvironment-dependent biomedical effects in varied oxidation stress-related diseases, but its molecular mechanism is unclear and its targeting molecule is unknown so far. Herein, we originally reveal that Fe-porphyrin is a H2-targeted molecule. We have demonstrated that the oxidized Fe-porphyrin in both free and protein-confining states can self-catalyze the hydrogenation/reduction by reacting with H2 to catalytically scavenge ∙OH, and can also catalytically hydrogenate to reduce CO2 into CO in the hypoxic microenvironment of in vitro simulation and in vivo tumor, confirming that Fe-porphyrin is a redox-related biosensor of H2 and H2 is an upstream signaling molecule of CO. These discoveries are favorable for deep understanding and exploration of profound biomedical effects of H2, and helpful for development of innovative drugs and hydrogen energy/agricultural materials.

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Publication history

Received: 15 July 2022
Accepted: 01 August 2022
Published: 13 August 2022

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© Tsinghua University Press 2022

Acknowledgements

Acknowledgements

We greatly appreciate financial support from the National Natural Science Foundation of China (Nos. 51872188 and 82172078), Shenzhen Science and Technology Program (No. RCJC20210706092010008), Special Funds for the Development of Strategic Emerging Industries in Shenzhen (No. 20180309154519685), and Center of Hydrogen Science, Shanghai Jiao Tong University, China.

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Email: nanores@tup.tsinghua.edu.cn

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