Role of Pink1-mediated mitophagy in adenomyosis

Minmin Chen; Wei Wang; Xianyun Fu; Yongli Yi; Kun Wang; Meiling Wang

doi:10.7717/peerj.16497

Role of Pink1-mediated mitophagy in adenomyosis

PeerJ. 2023 Nov 30:11:e16497. doi: 10.7717/peerj.16497. eCollection 2023.

Authors

Minmin Chen^#^{1

2

3}, Wei Wang^#¹, Xianyun Fu^{1

2

3}, Yongli Yi^{2

3}, Kun Wang^{1

2}, Meiling Wang^{1

2}

Affiliations

¹ College of Traditional Chinese Medicine, China Three Gorges University & Yichang Hospital of Traditional Chinese Medicine, Yichang, China.
² Third-grade Pharmacological Laboratory on Traditional Chinese Medicine, State Administration of Traditional Chinese Medicine, China Three Gorges University, Yichang, China.
³ College of Medicine and Health Sciences, China Three Gorges University, Yichang, China.

^# Contributed equally.

Abstract

Abstract background: Recent studies indicate that endometrial hypoxia plays a critical role in adenomyosis (AM) development. Mitochondria are extremely sensitive to hypoxic damage, which can result in both morphological and functional impairment. Mitophagy is a crucial mechanism for preserving mitochondrial quality by selectively removing damaged mitochondria, thus ensuring the proper functioning of the entire mitochondrial network. In response to hypoxia, PINK1 is activated as a regulator of mitophagy, but its role in AM requires further study.

Objective: To explore the potential mechanism of mitophagy mediated by PINK1 in the pathogenesis of AM.

Method: The study compared PINK1, Parkin, OPTIN, P62, and NDP52 protein expression levels in patients with or without AM using clinical specimens and an AM mouse model. Pathological changes were compared using HE staining. Immunofluorescence and western blot were used to detect protein expression levels. Endometrial stromal cells (ESC) were isolated and examined for mitophagy, protein expression level, and cell invasion ability.

Results: Both the endometrial tissue from patients with AM and AM ESC displayed an upregulation of protein levels for PINK1, Parkin, OPTIN, P62, and NDP52 when compared with the control group. Then, HE staining confirmed the successful establishment of the AM mouse model. Moreover, the ultrastructural analysis using transmission electron microscopy revealed that AM mice's endometrial glandular epithelial and stromal cells had exhibited swollen, deformed, and reduced mitochondria along with an increase in the number of lysosomes and mitochondrial autophagosomes. The protein levels of PINK1, Parkin, OPTIN, P62, and NDP52 in uterine tissue from AM mice were noticeably increased, accompanied by a considerable upregulation of ROS levels compared to the control group. In addition, cells in the AM group showed remarkably elevated mitophagy and invasion potentials compared to the control group. In contrast, the cell invasion ability decreased following PINK1 knockdown using the RNA interference technique.

Conclusion: The high levels of PINK1-mediated mitophagy have been found in AM. The upregulation in mitophagy contributes to mitochondrial damage, which may result in the abnormal invasion characteristic of AM.

Keywords: Adenomyosis; Mitophagy; PINK1.

MeSH terms

Adenomyosis*
Animals
Disease Models, Animal
Female
Humans
Hypoxia
Mice
Mitophagy* / genetics
Protein Kinases* / genetics
Ubiquitin-Protein Ligases / genetics

Substances

Protein Kinases
Ubiquitin-Protein Ligases
PTEN-induced putative kinase

Grants and funding

The funding for this research was provided by the National Natural Science Foundation of China (No.81973897). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.