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

YuFei Huang1, Yue Zhao1, HaoRan Liu1

  • 1Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, P. R. China.

Insights

GRIM-19 protein inhibits autophagy, a process linked to tumor metastasis. Decreased GRIM-19 in adenomyosis increases autophagy and cell invasion, suggesting a new therapeutic target for this condition.

Area of Science:

  • Cell Biology
  • Oncology
  • Gynecology

Background:

  • Adenomyosis involves endometrial invasion, similar to tumor metastasis.
  • GRIM-19 is a protein regulating cell death through the mitochondrial respiratory chain.
  • Cellular stress, like oxygen deprivation, can trigger autophagy, promoting tumor cell invasion and migration.

Purpose of the Study:

  • To investigate the role of GRIM-19 in regulating autophagy in adenomyosis.
  • To explore the relationship between GRIM-19 expression, autophagy, and cell invasion in adenomyosis.
  • To determine if the GRIM-19-AMPK-ULK1 pathway in adenomyosis mirrors its function in tumor tissues.

Main Methods:

  • Investigated GRIM-19's effect on autophagy in human endometrial and ISHIKAWA cells.
  • Analyzed the activation of the 5'-adenosine monophosphate-activated protein kinase-Unc-51 like autophagy activating kinase 1 (AMPK-ULK1) pathway.
  • Examined GRIM-19, AMPK, ULK1 expression, and autophagy levels in GRIM-19+/- mouse uterine tissues.

Main Results:

  • GRIM-19 negatively regulates autophagy.
  • Decreased GRIM-19 expression in adenomyosis correlates with increased autophagy and AMPK-ULK1 activation.
  • Upregulating GRIM-19 inhibits autophagy and reduces cell invasion and migration.
  • GRIM-19+/- mice showed increased AMPK, ULK1, and autophagy in uterine tissues.

Conclusions:

  • The GRIM-19-AMPK-ULK1 axis plays a crucial role in regulating autophagy in adenomyosis.
  • Adenomyosis exhibits tumor-like behavior regulated by autophagy, similar to tumor tissues.
  • This pathway presents a potential target for novel adenomyosis diagnosis and treatment strategies.

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