ミトコンドリアにおける水素シグナル伝達の再考：RieskeタンパクはH2作用の入口か下流センチネルか
This review examines recent evidence that molecular hydrogen (H2) suppresses mitochondrial Complex III activity through the Rieske iron-sulfur protein (RISP) and subsequent LONP1-mediated proteolysis, prompting a reassessment of whether RISP constitutes the primary molecular entry point for H2 signaling. From evolutionary and structural perspectives, RISP belongs to a broader family of hydrogenase-like mitochondrial redox proteins sharing ancient iron-sulfur architectures. Candidate proteins including succinate dehydrogenase subunit B (SDHB), Complex I iron-sulfur subunits, and CISD-family [2Fe-2S] proteins exhibit comparable redox properties and strategic positions within mitochondrial bioenergetic networks. The review organizes these candidates into a hierarchical, testable framework and proposes comparative structural, biochemical, and proteostatic approaches to identify the true molecular target of H2 in human mitochondria.
H2 may suppress mitochondrial Complex III via the Rieske iron-sulfur protein (RISP), triggering LONP1-dependent proteolysis; however, SDHB, Complex I iron-sulfur subunits, and CISD-family [2Fe-2S] proteins are proposed as alternative primary molecular targets warranting comparative investigation.
The delivery route is not clearly identifiable from this paper. For hydrogen intake, inhalation is the most efficient route; inhalation, however, carries explosion risk (empirical LFL of 10%; high-concentration devices are not recommended).
See also:
https://h2-papers.org/en/papers/41496215