Journal
CELL BIOCHEMISTRY AND FUNCTION
Volume 37, Issue 3, Pages 177-184Publisher
WILEY
DOI: 10.1002/cbf.3385
Keywords
ATM; autophagy; lipophagy; mitophagy; pexophagy; selective autophagy
Categories
Funding
- National Nature Science Foundation of China [81702651]
- China Postdoctoral Science Foundation Grant [2018M631884]
- Jilin Province Science and Technology Development Program [20180520123JH, 20190201275JC]
- Program from the education department of Jilin Province [JJKH20190075KJ]
- Program of Jilin provincial finance department [2018SCZ007]
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The ataxia-telangiectasia mutated (ATM) protein kinase is best known for its critical nuclear roles in the DNA damage response (DDR), cell cycle checkpoints, and the maintenance of gene stability. In this review, we highlight the multifaceted cytoplasmic functions of ATM in autophagy. We focused on the functions of ATM in nonselective autophagy in cancer. An Oncomine database analysis showed a tight association between ATM and autophagy in various cancers. In particular, its mechanisms in nonselective autophagy, those induced by ionizing radiation (IR), are illustrated in detail and involve the MAPK14 pathway, mTOR pathway, and Beclin1/PI3KIII complexes. Recently, an increasing number of studies revealed that autophagy could also be highly selective. We additionally emphasized the novel roles of ATM in selective autophagy, including mitophagy, pexophagy, and lipophagy. The regulation of these processes mainly involves ATM-PEX5, ATM-AMPK-TSC2-mTORC1-ULK1, PPM1D-ATM-MTOR, PINK I/Parkin, and NAD+/SIRT1. We aimed to provide new perspectives on the importance of ATM in the diverse field of autophagy. The intricate regulation of ATM in autophagy still requires further investigation, which would enhance our understanding of its role in cell dynamics and homeostasis. Significance of the study Our review highlighted the multifaceted cytoplasmic functions of ATM on autophagy. First, we focused on the functions of ATM in nonselective autophagy within cancer especially those induced by IR, involving the MAPK14 pathway, mTOR pathway, and Beclin1/PI3KIII complexes. These provided a theoretical understanding of tumour radiosensitivity and chemosensitivity. In addition, we emphasized the novel roles of ATM in selective autophagy, including mitophagy, pexophagy, and lipophagy. This review provides new perspectives on the importance of ATM in the diverse field of autophagy, which would provide more information on its role in whole cell dynamics and homeostasis.
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