Connexin a check-point component of cell apoptosis in normal and physiopathological conditions

Gap junction protein connexins (Cxs) play essential roles in cell homeostasis, growth, differentiation and death. Therefore, Cx dysfunction has been associated with many diseases and with tumor development. Cxs control cell apoptosis through different molecular mechanisms. First, gap junction channels classically facilitate the influx and flux of apoptotic signals between adjacent cells and hemichannels between the intracellular and extracellular environments. Second, recent studies demonstrate that Cx proteins, independently from their functional role through channels or hemichannels and in conjunction with their intracytoplasmic localization, may act as signaling effectors able to activate the canonical mitochondrial apoptotic pathway. In the present review, we dissected both functions of Cx in apoptosis, providing new avenues for apoptosis-mediated cancer therapy. •Potent innovative role of connexin in cell death has been proposed.•We dissect the connexin pathways involved in cell death apoptosis.•We highlight new roles of hemichannels and connexin proteins in this process.•The effect of antitumoral chemotherapeutic agents on these pathways is discussed.