Figure legends
Fig.1. H2Sn can transmit signals across cells, while S-sulfuration by MPST is restricted only inside the cells.
  1. H2S and H2Sn can pass through plasma membrane of the cell in which they are produced and reach the nearby cells as well as react with the targets inside the produced cell. H2S S-sulfurates the S-nitrosylated cysteine residues, while H2SnS-sulfurate the cysteine residues.
  2. MPST transfers sulfur from 3MP to targets inside the cell.
Fig. 2. S-sulfuration by H2Sn diffusion and that by MPST.
  1. MPST produces H2Sn which reach by diffusion to S-sulfurate H2S, cysteine, glutathione, and cysteine residues of proteins.
  2. MPST sulfur transfers from 3MP to H2S, cysteine, glutathione, and cysteine residues of proteins without being mediated by H2Sn.
This figure is produced by modifying Kimura et al., 2017.
Fig. 3. H2S is used for ATP production at physiological concentrations, while it inhibits cytochrome c oxidase at higher concentrations in mitochondria. H2S is metabolized by SQR, ETHE1, and rhodanese (TST) to thiosulfate through sulfite. Electrons are sent to coenzyme Q to complex IV though III and used for pumping out H+ from matrix to intermembrane space. ATP synthase produces ATP using the gradient of H+. In contrast, high concentrations of H2S suppress cytochrome c oxidase and the energy formation.
Fig. 4 Diseases caused by an excess amount of H2S and H2Sn in the central nervous system
A trisomy of choromosome 21, on which CBS is encoded, increases the levels of CBS in Down’s syndrome. Sulfur dioxygenase, which is encoded in ETHE1 and one of the enzymes metabolizing H2S and H2Sn, is defective in ethylmalonyl encephalopathy. Methylation of MPST gene increases the production of MPST in schizophrenia. Glycolysis is decreased by the suppression of several enzymes such as triosephosphate isomerase, phosphoglycerate kinase, phosphopyruvate hydratase. In these diseases cytochrome c oxidase is suppressed by high concentrations of H2S, resulting in the decreased production of ATP.
Fig. 5. Diseases caused by a lack of H2S or H2Sn in the central nervous system
S-sulfurated parkin in normal individuals is active, while parkin with the same cysteine residues being S-nitrosylated in PD brains is inactive. Mutant huntingtin suppresses the transcription of CSE gene from SP1, resulting in the decrease in the production of H2S. In HD animal model the activity of cystine/glutamate antiporter xCT is suppressed and glutathione levels are decreased, while those of ROS increased. The animal model of Alzheimer disease shows that H2S suppresses PI3K/Akt, while enhances the activity of STAT3. Both effects result in the decreased production of Aβ1-42 and suppression of inflammation. In some report the plasma levels of H2S are lower in patients of schizophrenia than normal individuals.