Int J Biol Sci 2021; 17(12):3080-3090. doi:10.7150/ijbs.63963 This issue

Review

ATM at the crossroads of reactive oxygen species and autophagy

Xiaochen Xie1,2, Ye Zhang1, Zhuo Wang1, Shanshan Wang1, Xiaoyou Jiang1, Hongyan Cui1, Tingting Zhou1, Zheng He3, Hao Feng4, Qiqiang Guo1✉, Xiaoyu Song1✉, Liu Cao1✉

1. College of Basic Medical Science, Key Laboratory of Medical Cell Biology, Ministry of Education, Key Laboratory of Liaoning Province, China Medical University, Shenyang, Liaoning Province, 110122, P. R. China.
2. Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, China Medical University, Shenyang, Liaoning, 110001, P. R. China.
3. Department of Radiation Oncology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, 110001, P. R. China.
4. Department of Ophthalmology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, 110001, P. R. China.

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Citation:
Xie X, Zhang Y, Wang Z, Wang S, Jiang X, Cui H, Zhou T, He Z, Feng H, Guo Q, Song X, Cao L. ATM at the crossroads of reactive oxygen species and autophagy. Int J Biol Sci 2021; 17(12):3080-3090. doi:10.7150/ijbs.63963. Available from https://www.ijbs.com/v17p3080.htm

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Abstract

Graphic abstract

Reactive oxygen species (ROS) are generally small, short-lived and highly reactive molecules, initially thought to be a pathological role in the cell. A growing amount of evidence in recent years argues for ROS functioning as a signaling intermediate to facilitate cellular adaptation in response to pathophysiological stress through the regulation of autophagy. Autophagy is an essential cellular process that plays a crucial role in recycling cellular components and damaged organelles to eliminate sources of ROS in response to various stress conditions. A large number of studies have shown that DNA damage response (DDR) transducer ataxia-telangiectasia mutated (ATM) protein can also be activated by ROS, and its downstream signaling pathway is involved in autophagy regulation. This review aims at providing novel insight into the regulatory mechanism of ATM activated by ROS and its molecular basis for inducing autophagy, and revealing a new function that ATM can not only maintain genome homeostasis in the nucleus, but also as a ROS sensor trigger autophagy to maintain cellular homeostasis in the cytoplasm.

Keywords: ATM, ROS, oxidative stress, autophagy, DNA damage response