Nature doi:10.1038/nature13147

Credit: KODI RAVICHANDRAN

PANX1 is a member of the newly identified family of plasma membrane channels that allows the passage of small molecules such as nucleotides, which are implicated in processes such as neutrophil activation. During apoptosis, nucleotides passing through PANX1 to the extracellular space act as signals to recruit phagocytes to complete the cell death program. Poon et al. set out to look for drug-like compounds that target PANX1 as these could prove useful for a range of diseases linked to these processes. Using a flow cytometry–based screen, the authors identified three potent inhibitors of PANX1 transport function. One of them was the quinolone-based antibiotic trovafloxacin, known to target bacterial topoisomerases. Several experiments, including patch clamping, indicated that trovafloxacin directly inhibits PANX1 and is specific for this channel. Thus, PANX1 may be the mammalian target associated with the serious side effects known to be caused by trovafloxacin use as an antibiotic. The authors found two additional quinolone antibiotics, difloxacin and tosufloxacin, with PANX1-targeting mechanisms similar to that of trovafloxacin. Using trovafloxacin, the authors next found a role for PANX1 in the regulation of the poorly characterized apoptotic cell disassembly into so-called apoptotic bodies and also defined an unappreciated early step of the apoptotic pathway involving PANX1-mediated downregulation of long string-like membrane blebs that they called 'apoptopodia'. These results help define a liability with quinolone antibiotics as well as an early step of apoptosis in which PANX1 acts in ordered disassembly.