Fig. 5: Cx43 regulates glucose uptake by interacting with IDH3α through the AMPK/TXNIP/GLUT1 pathway. | Cell Death & Disease

Fig. 5: Cx43 regulates glucose uptake by interacting with IDH3α through the AMPK/TXNIP/GLUT1 pathway.

From: Noncanonical role of astrocytic mitochondrial Cx43: suppressing IDH3α to sustain glycolytic homeostasis against depression

Fig. 5: Cx43 regulates glucose uptake by interacting with IDH3α through the AMPK/TXNIP/GLUT1 pathway.The alternative text for this image may have been generated using AI.

A Glucose uptake ability assessed by 2-NBDG uptake. n = 4. B, C Representative images of immunofluorescence staining and quantification of cell surface GLUT1 in Control and Cx43-KO astrocytes. Scale bar = 20 μm. n = 20 cells. D Western blot analysis of membrane GLUT1, p-AMPK, AMPK, Na-K ATPase and β-actin in Control and Cx43-KO astrocytes. Quantification of protein levels and p-AMPK/AMPK ratio are shown in (E, F). n = 4. G The intracellular ATP level of Control and Cx43-KO astrocytes, n = 4. H Western blot showing TXNIP stability in cycloheximide (CHX)-treated Control and Cx43-KO astrocytes. I Quantification of TXNIP expression in (H) at indicated times, n = 3. J Schematic diagram depicting the regulation of glucose uptake and glycolysis through the AMPK/TXNIP/GLUT1 pathway. K Schematic representation of the anti-Cx43 IP-MS experiment. L KEGG enrichment analysis of differential interacting proteins. M Dose–response curve of IDH3α and Cx43 interaction determined by MST. N The representative image of immunofluorescence staining for Cx43 (green), IDH3α (red) and DAPI (blue) in the PrL region. Scale bar, 10 μm. O Quantitative analysis of overlap coefficient of Cx43 and IDH3α. n = 20 cells. P The binding mode based on Cx43–IDH3α interaction dynamics simulation, overall view (left) and local view (right). The blue solid line represents hydrogen bonding, and the gray dotted line represents hydrophobicity. Q, R Western blot analysis of membrane GLUT1 and Na-K ATPase in Cx43-KO and IDH3αY126F mutant astrocytes. n = 4. S Glucose uptake ability assessed by 2-NBDG uptake. n = 3. T The intracellular ATP level of Cx43-KO and IDH3αY126F mutant astrocytes. n = 3. U The real-time changes of ECAR trace in astrocytes, and the quantification (V) of basal glycolysis and glycolytic capacity. n = 4. Two-tailed Student’s t test was performed between two groups; two-way ANOVA followed by the Geisser–Greenhouse correction in (I); one-way ANOVA followed by Dunnett’s multiple comparisons test in multiple groups. All data represent the mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.

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