Biology subjects

Ida, T.

Publications and source records attributed to Ida, T..

3 recordsLinked to original sources

bioRxiv2024

Mitochondria Regulate the Cell Fate Decisions of Megakaryocyte-Erythroid Progenitors

Recent studies highlight the critical role of mitochondria in hematopoiesis, especially in stem cell function and erythroid maturation. To explore mitochondrial contributions to cell lineage commitment of hematopoietic progenitors, we utilized Cars2 mutant mice, an ideal model for this purpose. CARS2, a mitochondrial isoform of cysteinyl-tRNA synthetase, has cysteine persulfide synthase (CPERS) activity. Our new mouse model, with reduced CPERS activity, showed that the Cars2 mutation led to mitochondrial inhibition and anemia by suppressing erythroid commitment in megakaryocyte-erythroid progenitors (MEPs). This suppression was reproduced using mitochondrial electron transport chain inhibitors. We identified two distinct MEP populations based on the mitochondrial content: mitochondria-rich MEPs favored erythroid differentiation, while the mitochondria-poor MEPs favored megakaryocyte differentiation. These findings reveal critical contributions of mitochondria to the MEP lineage selection, acting as a "mitochondrial navigation" for lineage commitment.

cell biology↗

bioRxiv2024

Glutathione supersulphide regulates T-cell receptor signalling

Immunometabolism regulates functions and fates of immune cells including T cells. Supersulphides, which are universal metabolites containing catenated sulphur atoms, have various physiological functions based on their unique redox properties. Here we found that activation of T-cell receptor (TCR) signalling was accompanied by supersulphide decrease, which suggests a regulatory contribution of sulphur metabolism to immune function. Consistently, inhibiting supersulphide synthesis facilitated TCR activation and exacerbated allergen-induced type 2 inflammation in mice. Supplementation with glutathione trisulphide (GSSSG), a major endogenous supersulphide, suppressed TCR signalling in naive CD4+ T cells and their differentiation and effectively alleviated the inflammation. Docking simulation revealed interaction of GSSSG with CD3{varepsilon} chain in the TCR/CD3 complex, which was supported by mass spectrometry detection of persulphidated glutathionylation at a functionally important CXXC motif of CD3{varepsilon} chain. This study identified a new post-translational modification with supersulfides and demonstrated a critical contribution of sulphur metabolism to TCR signalling regulation.

biochemistry↗

bioRxiv2023

Growth inhibitory factor/metallothionein-3 is a sulfane sulfur-binding protein

Cysteine-bound sulfane sulfur atoms in proteins have received much attention as key factors in cellular redox homeostasis. However, the role of sulfane sulfur in zinc regulation has been underinvestigated. We report here that cysteine-bound sulfane sulfur atoms serve as ligands to hold and release zinc ions in growth inhibitory factor (GIF)/metallothionein-3 (MT-3) with an unexpected C-S-S-Zn structure. Oxidation of such a zinc/persulfide cluster in Zn7GIF/MT-3 results in the release of zinc ions, and intramolecular tetrasulfide bridges in apo-GIF/MT-3 efficiently undergo S-S bond cleavage by thioredoxin to regenerate Zn7GIF/MT-3. Three-dimensional molecular modeling confirmed the critical role of the persulfide group in the thermostability and Zn-binding affinity of GIF/MT-3. The present discovery raises the fascinating possibility that the function of other Zn-binding proteins is controlled by sulfane sulfur.

biochemistry↗