Hydrogen Targets Specific Protein in Cells, Triggering Health Benefits
- Authors
- Shuto Negishi, Mikako Ito, Tomoya Hasegawa, Hikaru Otake, Bisei Ohkawara, Akio Masuda, Hiroyuki Mino, Tyler W LeBaron, Kinji Ohno
- Journal
- Redox Biology
- Year
- 2025
- DOI
- 10.1016/j.redox.2025.103952
- Study Type
- Cell Culture
- Outcome
- Positive
- Peer Reviewed
- Yes
- Country
- Japan
- Health Condition
- Mitochondrial Dysfunction
- Body System
- Cellular
TL;DR
Hydrogen directly interacts with mitochondrial proteins, triggering protective stress-response pathways and acting as a biological signaling molecule.
Key Finding
Molecular hydrogen directly targets and promotes the degradation of the Rieske iron-sulfur protein (RISP) in mitochondria by activating a cellular cleanup enzyme, triggering a mitochondrial stress response rather than functioning solely as an antioxidant.
Summary
Researchers discovered that molecular hydrogen (H2) is not biologically inert as previously thought, but instead actively targets a specific protein called the Rieske iron-sulfur protein (RISP) found in mitochondria (the energy-producing structures in cells). When cells or mouse liver were exposed to hydrogen water, the hydrogen triggered the breakdown of RISP through a cellular cleanup mechanism, which in turn activated a stress response in the mitochondria. This suggests hydrogen works as a signaling molecule rather than simply as an antioxidant.
Practical Takeaway
This cell culture study provides early evidence that hydrogen water may work through a previously unknown mechanism involving mitochondrial signaling. However, these findings are from laboratory experiments only and have not been tested in humans, so their relevance to actual health effects remains unclear. Further research in animal models and human trials would be needed to understand whether this mechanism translates to any practical health benefits.
Abstract
The mechanisms underlying the biomedical effects of molecular hydrogen (H2) remain poorly understood and are often attributed to its selective reduction of hydroxyl radicals, based on the long-held notion that H2 is biologically inert. We demonstrate that H2 is biologically active, specifically targeting the Rieske iron-sulfur protein (RISP). We first observed that H2 induces the mitochondrial unfolded protein response (UPRmt) in cultured cells exposed to H2 and in mouse liver after H2 water administration. H2 suppressed electron transport chain complex III activity in mouse liver homogenates to 78.5 % within 2 min. Given the evolutionary link with hydrogenases, we examined RISP as a potential target of H2. We found that H2 promotes RISP degradation within 1 h in cultured cells by activating mitochondrial Lon peptidase 1 (LONP1). Loss of RISP and subsequent UPRmt induction may explain the pleiotropic and paradoxical effects of H2. These findings identify RISP as a primary target of H2, demonstrating that H2 is biologically active as a signaling molecule.