Fig. 6: Disulfide-bridge formation between IDH3γ Cys148 and Cys284 changes the tetramerization interface of IDH3.

A Quantification of IDH3γ Cys148 oxidation as the percentage of occupancy in different tissues from n = 5 biologically independent 16-week-old male C57BL/6 J mice. Data are obtained from the Oximouse database. subQ subcunateous fat, SKM skeletal muscle, epi epididymal fat, BAT brown adipose tissue. mean ± SEM. B Structure of the IDH3α/γ dimer with main functional sites. Citrate, Mg²⁺ and ADP are shown as ball and sticks. C Root mean square deviation (RMSD) plot for the clasp region for each system/replica. D Selected clasp regions from the two simulations showing substantial conformational changes (noSSr2, noSSr5, in blue for α subunit and red for γ subunit) and one stable reference (SSr2, in cyan for α subunit and orange for γ subunit) superimposed onto the tetrameric structure of IDH3 (IDH3α/γ / IDH3α/β, PDB ID: 7CE3, clasp regions in gray). For clarity, the zoomed images do not show the IDH3α/β dimer. E Stress difference plot. Residues were renumbered consecutively from 0. The difference between the systems without (noSS) and with disulfide bridge (SS) was obtained by computing the difference between their averages, the standard deviations for each residue in the averaged curves noSS and SS were propagated to the difference (gray error bars). Residues with statistically relevant (p < 0.0001 in a Student’s t-test on the two series with n = 50 data points) changes in the total stress between noSS and SS are highlighted and mapped onto the structure. Cysteines involved in the disulfide-bond are circles in yellow. This figure is related to Supplemental Fig. 4. Source data are provided as a Source Data file.