2. Academic Validation
  3. Circ-CIMIRC inhibition alleviates CIH-induced myocardial damage via FbxL4-mediated ubiquitination of PINK1

Circ-CIMIRC inhibition alleviates CIH-induced myocardial damage via FbxL4-mediated ubiquitination of PINK1

  • iScience. 2024 Jan 20;27(2):108982. doi: 10.1016/j.isci.2024.108982.
Runhua Wu 1,  Fengsheng Xu 1,  Jingyi Li 1,  Feng Wang 1,  Naijie Chen 1,  Xiaoting Wang 2,  Qin Chen 2
Affiliations

Affiliations

  • 1 College of Integrated Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350100, China.
  • 2 Clinical Skills Teaching Center, Fujian University of Traditional Chinese Medicine, Fuzhou 350100, China.
PMID: 38333696 DOI: 10.1016/j.isci.2024.108982
Abstract

Obstructive sleep apnea (OSA) is a common sleep disordered breathing diseases that characterized by chronic intermittent hypoxia (CIH). This work aimed to explore the role of circ-CIMIRC in CIH-induced myocardial injury. CIH aggravated myocardial tissue damage in rats. Circ_CIMIRC overexpression promoted Apoptosis and reduced the colocalization of Tom20 and Parkin and Mitophagy in CIH-treated H9c2 cells. Additionally, FbxL4 interacted with PINK1, FbxL4 silencing reduced PINK1 ubiquitination in H9c2 cells. Two major ubiquitination sites (K319 and K433) were responsible for ubiquitination of PINK1. Circ_CIMIRC promoted FbxL4-mediated ubiquitination and degradation of PINK1. Furthermore, circ_CIMIRC inhibition alleviated the pathological damage, fibrosis and Apoptosis of myocardial tissues, reduced oxidative stress in CIH rats. In conclusion, circ_CIMIRC silencing repressed FbxL4-mediated ubiquitination and degradation of PINK1 and then enhanced PINK1/Parkin-mediated Mitophagy, thereby alleviating myocardial damage in CIH rats. Thus, circ_CIMIRC may be a potential strategy to alleviate CIH-induced myocardial damage.

Keywords

Cell biology; Molecular biology.

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