Dai and Hyman Reveal Condensate‑Driven ROS Mechanism
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- Yifan Dai and Anthony A. Hyman reported in the Journal of the American Chemical Society that biomolecular condensates generate reactive oxygen species spontaneously without enzymes, driven by an interfacial electric field created by ion imbalance.
- Biomolecular condensates possess an alkaline environment that promotes deprotonation of tyrosine residues, releasing electrons that combine with oxygen to form superoxide radicals and hydrogen peroxide.
- Hydrogen peroxide produced in condensates can damage proteins and accelerate pathways leading to neurodegenerative diseases such as Alzheimer's and ALS.
- Condensates become progressively more alkaline as hydrogen peroxide formation consumes protons, creating a self‑reinforcing chemical environment.
- X N. Zare and Yifan Dai demonstrated in a separate JACS paper that biomolecular condensates can drive nitrogen‑cycling redox reactions without enzymes, modulating reactive nitrogen species.
- The researchers argue that the electrical field at the condensate–cell interface is the primary driving force for these redox reactions, analogous to the chemistry of batteries.
Why it matters: The finding gives disease researchers a new molecular target for intervening in ROS‑driven neurodegeneration, while highlighting condensates as active chemical hubs that could be modulated to prevent protein damage, potentially shifting therapeutic strategies away from mitochondria‑centric approaches and offering a fresh avenue for drug development.
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