Fig. 9 | Nature Communications

Fig. 9

From: Corticosteroids inhibit Mycobacterium tuberculosis-induced necrotic host cell death by abrogating mitochondrial membrane permeability transition

Fig. 9

Model depicting a novel mode of Mtb-induced cell death and its chemical inhibition. Phagocytosis of Mtb leads to p38 MAPK phosphorylation and hexokinase II (HKII) dissociation, which seems to open the mitochondrial permeability transition pore (mPTP) subsequently leading to necrotic cell death which can be monitored by high-mobility group protein B1 (HMGB1) release. Several substances interfere with this pathway to protect cells. Dexamethasone or BI653048 treatment inhibits p38 MAPK phosphorylation via the glucocorticoid receptor (GR) and MAPK phosphatase 1 (MKP-1). Direct p38 MAPK blockade using doramapimod has a similar cytoprotective effect. p38 MAPK promotes dissociation of hexokinase II (HKII) from the mitochondrion leading to ATP depletion. Cyclosporin A directly interferes with mPTP opening via inhibition of cyclophillin D, a regulator of the mPTP. VDAC voltage-dependent anion channel

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