Dram1 regulates DNA damage-induced alternative autophagy
Authors:Meruna Nagata1, Satoko Arakawa1, Hirofumi Yamaguchi1, Satoru Torii1, Hazuki Endo1, Masatsune Tsujioka1, Shinya Honda1, Yuya Nishida1, Akimitsu Konishi1,2, Shigeomi Shimizu1
1 Department of Pathological Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
2 Present address: Department of Biochemistry, Gunma University Graduate School of Medicine, 3-39-22 Showa, Maebashi, Gunma 371-8511 Japan.
Keywords:
alternative autophagy, DNA damage response, genotoxic stress, p53, Dram1.
Abbreviations:
Atg – autophagy related,
CLEM – correlative light electron microscopy,
DKO – double knock out,
Dram1 – dagame-regulated autophagy modulator 1,
EM – electron microscopy,
KO – knock out,
LC3 – light chain 3,
MEF – mouse embryonic fibroblast,
shRNA – short hairpin RNA,
STS – staurosporine,
WT – wild type.
Corresponding Author(s):
Conflict of interest statement:
The authors declare that they have no competing interests that might be perceived to influence the results and/or discussion reported in this paper.
Please cite this article as:
Meruna Nagata, Satoko Arakawa, Hirofumi Yamaguchi, Satoru Torii, Hazuki Endo, Masatsune Tsujioka, Shinya Honda, Yuya Nishida, Akimitsu Konishi, Shigeomi Shimizu (2018). Dram1 regulates DNA damage-induced alternative autophagy. Cell Stress 2(3): 55-65. doi: 10.15698/cst2018.03.127
© 2018 Nagata et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Abstract:
Autophagy is an evolutionarily conserved process that degrades subcellular constituents. Mammalian cells undergo two types of autophagy; Atg5-dependent conventional autophagy and Atg5-independent alternative autophagy, and the molecules required for the latter type of autophagy are largely unknown. In this study, we analyzed the molecular mechanisms of genotoxic stress-induced alternative autophagy, and identified the essential role of p53 and damage-regulated autophagy modulator (Dram1). Dram1 was sufficient to induce alternative autophagy. In the mechanism of alternative autophagy, Dram1 functions in the closure of isolation membranes downstream of p53. These findings indicate that Dram1 plays a pivotal role in genotoxic stress-induced alternative autophagy.