Arginyltransferase1 mediates cell death by a mitochondria‐dependent pathway

Abstract

The regulation of cell death in eukaryotic cells is a fundamental process for the adaptation to stress or for the response to signals. Recent studies showed that an evolutionarily conserved enzyme, arginyltransferase1 (ATE1), which is known to induce protein degradation via the N-end rule pathway, is also involved in cell death. Particularly, ATE1 is elevated under acute oxidative stress conditions and is causing apoptosis in yeast and mammalian cells. However, how does ATE1 mediate cell death remains unknown. Here, by using budding yeast as a test model, we found that ATE1 is colocalized with mitochondria under oxidative stress, and that this translocation is essential for ATE1-induced apoptosis. We also found that the mutations which disrupt the arginylation activity also compromise the ATE1-induced cell death, without affecting its mitochondrial localization. Furthermore, we found that the ATE1-mediated cell death is not dependent on mitochondrial ETC activity or the caspase pathway. Rather, we found that ATE1-mediated cell death is dependent on the mitochondrial permeability pore and the apoptosis-inducing factor. We conclude that ATE1 is a novel apoptosis-regulator that utilizes specific mitochondrial pathways.