リスケ鉄硫黄タンパク質は分子状水素の主要な標的である
The biomedical mechanisms of molecular hydrogen (H₂) have long been attributed primarily to hydroxyl radical scavenging, with H₂ generally considered biologically inert. This study challenges that view by identifying the Rieske iron-sulfur protein (RISP) as a direct molecular target of H₂. Mitochondrial unfolded protein response (UPRmt) was observed both in cultured cells exposed to H₂ and in mouse liver following hydrogen-rich water administration. In mouse liver homogenates, H₂ reduced electron transport chain complex III activity to 78.5% within 2 minutes. Drawing on the evolutionary relationship between RISP and hydrogenases, the authors found that H₂ activates mitochondrial Lon peptidase 1 (LONP1), leading to RISP degradation within 1 hour in cultured cells. The resulting loss of RISP and subsequent UPRmt induction provide a mechanistic framework for the pleiotropic and paradoxical biological effects of H₂, establishing it as an active signaling molecule rather than a passive antioxidant.
H₂ activates mitochondrial Lon peptidase 1 (LONP1), promoting degradation of the Rieske iron-sulfur protein (RISP) within 1 hour. This suppresses electron transport chain complex III activity and triggers the mitochondrial unfolded protein response (UPRmt), positioning H₂ as a biologically active signaling molecule.
This study combines multiple delivery routes. As a general principle, the most efficient route for routine hydrogen intake is inhalation. Inhalation carries explosion risk (empirical LFL of 10%; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).
See also:
https://h2-papers.org/en/papers/41330217