Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Apr 12:9:668735.
doi: 10.3389/fcell.2021.668735. eCollection 2021.

Autophagic Organelles in DNA Damage Response

Jeongha Kim  1 , Sungmin Lee  1 , Hyunwoo Kim  1 , Haksoo Lee  1 , Ki Moon Seong  2 , HyeSook Youn  3 , BuHyun Youn  1   4
Affiliations
Review

Autophagic Organelles in DNA Damage Response

Jeongha Kim et al. Front Cell Dev Biol. .

Abstract

Autophagy is an important subcellular event engaged in the maintenance of cellular homeostasis via the degradation of cargo proteins and malfunctioning organelles. In response to cellular stresses, like nutrient deprivation, infection, and DNA damaging agents, autophagy is activated to reduce the damage and restore cellular homeostasis. One of the responses to cellular stresses is the DNA damage response (DDR), the intracellular pathway that senses and repairs damaged DNA. Proper regulation of these pathways is crucial for preventing diseases. The involvement of autophagy in the repair and elimination of DNA aberrations is essential for cell survival and recovery to normal conditions, highlighting the importance of autophagy in the resolution of cell fate. In this review, we summarized the latest information about autophagic recycling of mitochondria, endoplasmic reticulum (ER), and ribosomes (called mitophagy, ER-phagy, and ribophagy, respectively) in response to DNA damage. In addition, we have described the key events necessary for a comprehensive understanding of autophagy signaling networks. Finally, we have highlighted the importance of the autophagy activated by DDR and appropriate regulation of autophagic organelles, suggesting insights for future studies. Especially, DDR from DNA damaging agents including ionizing radiation (IR) or anti-cancer drugs, induces damage to subcellular organelles and autophagy is the key mechanism for removing impaired organelles.

Keywords: DNA damage response; ER-phagy; mitophagy; ribophagy; therapeutic approach.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Schematic representation of removing damaged mitochondria by mitophagy. The accumulation of damaged mitochondria is removed by mitophagy when mitochondria are exposed to DNA damage factors such as ionizing radiation, ROS, and drug.
FIGURE 2
FIGURE 2
Schematic representation between ER stress factor and ER-phagy. The figure represents a signaling pathway of ER-phagy while damaged ER is engulfed by autophagosome. When ER stress is induced by DNA damage, the IRE1a, PERK, and ATF6 signaling pathways are activated, resulting in the formation of autophagosomes.
FIGURE 3
FIGURE 3
Schematic representation of removing damaged ribosome by ribophagy. The accumulation of damaged ribosome is removed by ribophagy. For the most part, the ribosome is related to RNA but ribosome biogenesis is affected by DNA. DNA damage interrupts ribosome biogenesis and decreases the stability of rDNA. ZNHIT3 and NUFIP1 have been suggested as a major factors of ribophagy induction in mammalian cells.
See this image and copyright information in PMC

References

    1. Adachi Y., Yamamoto K., Okada T., Yoshida H., Harada A., Mori K. (2008). ATF6 is a transcription factor specializing in the regulation of quality control proteins in the endoplasmic reticulum. Cell Struct. Funct. 33 75–89. 10.1247/csf.07044 - DOI - PubMed
    1. Alao J. P., Sunnerhagen P. (2009). The ATM and ATR inhibitors CGK733 and caffeine suppress cyclin D1 levels and inhibit cell proliferation. Radiat. Oncol. 4:51. 10.1186/1748-717x-4-51 - DOI - PMC - PubMed
    1. Alexander A., Cai S. L., Kim J., Nanez A., Sahin M., MacLean K. H., et al. (2010). ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS. Proc. Natl. Acad. Sci. U.S.A. 107 4153–4158. 10.1073/pnas.0913860107 - DOI - PMC - PubMed
    1. Anding A. L., Baehrecke E. H. (2017). Cleaning house: selective autophagy of organelles. Dev. Cell 41 10–22. 10.1016/j.devcel.2017.02.016 - DOI - PMC - PubMed
    1. Atkins C., Liu Q., Minthorn E., Zhang S. Y., Figueroa D. J., Moss K., et al. (2013). Characterization of a novel PERK kinase inhibitor with antitumor and antiangiogenic activity. Cancer Res. 73 1993–2002. 10.1158/0008-5472.Can-12-3109 - DOI - PubMed

LinkOut - more resources