**14.7. Interplay among apoptosis, necrosis/necroptosis and autophagy**

Cell death process *in vivo* involves a complex interaction among apoptosis, necrosis/necroptosis and autophagy [78]. In some situations, a specific stimulus triggers only one mechanism, but in other cases, the same stimulus can evoke more than one cell demise machinery. Therefore, several mechanisms can coexist within a cell, but only one will predominate over the others. The decision to undergo apoptosis, necrosis/necroptosis or autophagy depends on various factors: energy/ATP availability, extent of the stress and the damage and presence of inhibitors of particular pathways (e. g. caspases inhibitors) [214]. ATP depletion activates autophagy, but if autophagy fails to maintain energy levels, necrosis/necroptosis results [215]. Apoptosis is usually triggered with sufficient ATP levels to trigger caspases. If the damage is severe necrosis prevails over apoptosis [216,217]. Hence, apoptosis is the first choice in most circumstances and necroptosis is triggered only as a backup alternative to guarantee that cell death takes place. However, in some cases (e.g. viral infection) TNF-mediated necroptosis predominate [218]. Apoptosis can inhibit autophagy through Bcl-2-mediated sequestration [155,156] or caspase-dependent cleavage of Beclin 1 [219,220,220], and conversely, autophagy can inhibit apoptosis by caspase-8 degradation [221].
