Decreased expression of GRIM-19 induces autophagy through the AMPK/ULK1 signaling pathway during adenomyosis

The processes underlying adenomyosis are similar to those of tumor metastasis, and it is defined as progressive invasion by the endometrium and the subsequent creation of ectopic lesions. GRIM-19 regulates cell death via the mitochondrial respiratory chain. Stress following oxygen deprivation can in...

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Bibliographic Details
Published in:Biology of reproduction 2022-10, Vol.107 (4), p.956-966
Main Authors: Huang, YuFei, Zhao, Yue, Liu, HaoRan, Yang, Yang, Cheng, LaiYang, Deng, XiaoHui, Chao, Lan
Format: Article
Language:English
Subjects:
adenomyosis
Adenosine kinase
AMP
AMPK
Autophagy
Cell death
Cell migration
Electron transport
Endometrium
GRIM-19
GRIM-19 +/– mice
Kinases
Metastases
RESEARCH ARTICLE
Respiration
Signal transduction
Tumors
ULK1
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Summary:The processes underlying adenomyosis are similar to those of tumor metastasis, and it is defined as progressive invasion by the endometrium and the subsequent creation of ectopic lesions. GRIM-19 regulates cell death via the mitochondrial respiratory chain. Stress following oxygen deprivation can induce tumor cell autophagy, leading to cell invasion and migration. Here, we revealed that GRIM-19 negatively regulates autophagy, and, at least in adenomyosis, decreased expression of GRIM-19 is accompanied by an increased level of autophagy and 5′-adenosine monophosphate-activated protein kinase-Unc-51 like autophagy activating kinase 1 (AMPK-ULK1) activation. Upregulation of GRIM-19 expression in human primary endometrial cells and ISHIKAWA cells inhibits autophagy via the AMPK-ULK1 pathway and helps control cell invasion and migration. In addition, we also identified increased expression of AMPK and ULK1, and higher levels of autophagy in the uterine tissues of GRIM-19+/– mice. Importantly, the function of the GRIM-19-AMPK-ULK1 axis in regulating autophagy in adenomyosis is similar to that of tumor tissues, which may help elucidate the regulation of adenomyosis tumor-like behavior, and is expected to help identify novel targets for the diagnosis and treatment of adenomyosis. Summary Sentence GRIM-19 knockdown increased autophagy and AMPK/ULK expression, whereas GRIM-19 overexpression reduced their expression in vitro; these observations were validated in a GRIM-19 allelic gene heterozygotes mouse model.
ISSN:0006-3363
1529-7268
DOI:10.1093/biolre/ioac151