Autophagy prevents autophagic cell death of Tetrahymena in response to oxidative stress

Autophagy is a major cellular pathway used to degrade long‐lived proteins or organelles that may be damaged by increased reactive oxygen species generated by the cellular stress and typically enhances cell survival, but it may also act to promote cell death under different conditions. The mechanism underlying the paradox that autophagy functions in some instances to promote survival but in others to induce cell death remains unclear. Here we show that Tetrahymena cells exert increased membrane‐bound vacuoles characteristic of autophagosomes followed by massive cell death after exposure to hydrogen peroxide. Inhibition of autophagy by chloroquine or the PI‐3 kinase inhibitor wortmannin significantly augments cell death under oxidative stress. Treatment of the cells with caspase inhibitors blocks classic type I cell death and induces type II cell death (referred to as autophagic cell death) in a caspase‐independent pathway. Importantly, analyses of cells treated with chloroquine or wortmannin show a parallel suppression of autophagy associated with increased autophagic cell death in the presence of caspase inhibitors. Taken together, our results suggest that autophagy plays an essential role in preventing the initiation of autophagic cell death of Tetrahymena exposed to oxidative stress.