Inhibition of the mitochondrial F1F0-ATPase by ligands of the peripheral benzodiazepine receptor

Although PK11195 binds to the peripheral benzodiazepine receptor with nanomolar affinity, significant data exist which suggest that it has another cellular target distinct from the PBR. Here we demonstrate that PK11195 inhibits F1F0-ATPase activity in an OSCP-dependent manner, similar to the pro-apoptotic benzodiazepine Bz-423. Importantly, our data indicate that cellular responses observed with micromolar concentrations of PK11195, which are commonly attributed to modulation of the PBR, are likely a direct result of mitochondrial F1F0-ATPase inhibition.

Graphical abstractPBR-ligand PK-11195 inhibits F1F0-ATPase activity in an OSCP-depender manner, similar to the pro-apoptotic benzodiazepine Bz-423.Figure optionsDownload full-size imageDownload as PowerPoint slide