The disassembly of death

Abstract

During the cell-death program known as apoptosis, cells break up into membrane-bound fragments. It emerges that this process is controlled by the protein pannexin 1 and can be deregulated by an antibiotic. See Article p.329 The pannexin 1 channel on the plasma membrane of apoptotic cells mediates the release of find-me molecular signals that attract phagocytic cells tasked to clear away the dead cells. In an unbiased screen of small molecules, Kodi Ravichandran and colleagues identify the quinolone antibiotic trovafloxacin as a direct inhibitor of the pannexin 1 channel activity, which results in dysregulated fragmentation of apoptotic cells. This work establishes an essential role for pannexin channels in orderly disassembly of apoptotic cells, and could also re-invigorate interest in quinolone antibiotics without cross-reactivity with the pannexin 1 channel, which may explain the particular toxicity that emerged during clinical trials of trovafloxacin.