Switch between apoptosis and autophagy: radiation-induced endoplasmic reticulum stress?
The induction of cell death by radiation has largely been attributed to pro-apoptotic mechanisms. Autophagy, an alternative form of programmed cell death, has recently been shown to contribute significantly to anti-neoplastic effects of radiation therapy. In light of this, ER stress has been shown to trigger both apoptosis and autophagy, and act as an important mediator linking the two programmed cell death pathways. Recent data reveal that ER stress leads to activation of autophagosome formation with LC3 conversion via either PERK-eIF2a pathway or IRE1-JNK pathway. In this focused review, we summarize the main molecular mediators that control cellular "switches" between apoptosis and autophagy pathways by utilizing radiation therapy as a model.
Moretti
Luigi
L
Department of Radiation Oncology, Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee 37232, USA.
Cha
Yong I
YI
Niermann
Kenneth John
KJ
Lu
Bo
B
D000818:Animals; D017209:Apoptosis / Q000502:physiology / Q000528:radiation effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism / Q000528:radiation effects; D001343:Autophagy / Q000502:physiology / Q000528:radiation effects*; D004721:Endoplasmic Reticulum / Q000502:physiology / Q000528:radiation effects*; D004722:Endoribonucleases / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism / Q000528:radiation effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000528:radiation effects; D015398:Signal Transduction / Q000502:physiology / Q000528:radiation effects; D019892:eIF-2 Kinase / Q000378:metabolism / Q000528:radiation effects
D051017:Apoptosis Regulatory Proteins; D004722:Endoribonucleases; D008565:Membrane Proteins; D017346:Protein Serine-Threonine Kinases; D019892:eIF-2 Kinase; C403982:ERN2 protein, human