Extended Data Fig. 10: Model for Gboxin-mediated OXPHOS inhibition in GBM cells.
From: Gboxin is an oxidative phosphorylation inhibitor that targets glioblastoma
Top, high pH in mitochondrial matrix of GBM cells, and high inner mitochondrial membrane (IMM) potential, leads to the persistent accumulation of positively charged Gboxin, owing to blunted mPTP activity. At a high local concentration, Gboxin associates with multiple OXPHOS proteins and inhibits complex V activity, causing cell death. Bottom, in wild-type Gboxin-resistant cells, mPTP function stabilizes mitochondrial membrane potential and maintains a lower pH. This limits mitochondrial Gboxin accumulation, and thus limits OXPHOS inhibition and sustains cell survival. mPTP (green cylinder) is depicted adjacent to F0F1 ATPase complex V. The precise nature and contribution of complex V to mPTP remains unresolved.
