Related Experiment Video
Updated: Sep 9, 2025
Protection of H9c2 Myocardial Cells from Oxidative Stress by Crocetin via PINK1/Parkin Pathway-Mediated Mitophagy
Published on: May 26, 2023
ER stress disrupts MFN2-related mitophagy via HRD1-PINK1/ parkin axis in bovine embryos
Shu-Ming Shi1, Li-Ying Liu1, Zhi-Chao Chi1
1College of Animal Sciences, Jilin University, Changchun, 130062, Jilin Province, China.
Abstract:
The endoplasmic reticulum and mitochondria are interconnected through the MAM structure, and mitochondrial fusion protein 2 (MFN2) is a key regulatory factor. In this study, tunicamycin (TM) was used to induce endoplasmic reticulum stress in bovine embryos to explore its effects on MFN2 expression, mitochondrial function and mitochondrial autophagy. The results showed that TM treatment significantly reduced the blastocyst rate and proliferation capacity of embryos, inhibited the expression of pluripotency genes (SOX2, CDX2, OCT4), and upregulated key proteins of the UPR pathway. The expression of MFN2 and MAM region E3 ubiquitin ligase (HRD1) was significantly increased, PINK1 expression was downregulated, and Parkin localization on the mitochondrial membrane was reduced. Colocalization analysis and the reduction of LC3-II ratio indicated that mitochondrial autophagy was blocked. At the same time, mitochondrial membrane potential, ATP content and functional genes (PGC-1, TFAM) expression were downregulated, OXPHOS key enzymes were inhibited, and glycolysis was compensated. The mitochondrial apoptosis marker cytochrome C was released, Caspase3 was upregulated, and the PI positive rate increased. In summary, ER stress inhibits mitophagy through HRD1 -mediated PINK1 degradation, leading to the accumulation of mitochondrial damage, aggravating energy metabolism disorders and apoptosis, and ultimately inhibiting the in vitro development of bovine embryos.
Insights
Endoplasmic reticulum stress induced by tunicamycin impairs bovine embryo development by blocking mitochondrial autophagy. This leads to mitochondrial damage, energy dysfunction, and apoptosis, hindering embryo quality.
Area of Science:
- Cell Biology
- Developmental Biology
- Mitochondrial Biology
Background:
- The endoplasmic reticulum (ER) and mitochondria are crucial organelles with interconnected functions.
- Mitochondrial fusion protein 2 (MFN2) plays a key role in ER-mitochondria crosstalk via the Mitochondria-Associated Membranes (MAM) structure.
Purpose of the Study:
- To investigate the impact of tunicamycin (TM)-induced ER stress on bovine embryo development.
- To analyze the effects on MFN2 expression, mitochondrial function, and mitophagy.
Main Methods:
- Bovine embryos were treated with tunicamycin (TM) to induce ER stress.
- Assessed blastocyst rates, proliferation capacity, and pluripotency gene expression (SOX2, CDX2, OCT4).
- Evaluated Unfolded Protein Response (UPR) pathway proteins, MFN2, HRD1, PINK1, Parkin, and mitochondrial autophagy markers (LC3-II).
Main Results:
- TM treatment reduced blastocyst rates and embryo proliferation, inhibiting pluripotency genes.
- UPR pathway proteins were upregulated; MFN2 and HRD1 expression increased, while PINK1 decreased.
- Mitophagy was blocked (reduced LC3-II ratio), leading to decreased mitochondrial membrane potential, ATP, and PGC-1/TFAM expression.
- Mitochondrial dysfunction was evident, with OXPHOS inhibition, glycolysis compensation, and increased apoptosis markers (cytochrome C, Caspase3).
Conclusions:
- ER stress inhibits mitophagy via HRD1-mediated PINK1 degradation, accumulating mitochondrial damage.
- This exacerbates energy metabolism disorders and apoptosis, ultimately impairing in vitro development of bovine embryos.
More Related Videos
Related Concept Videos
01:31Regulation of the Unfolded Protein Response
01:37The Unfolded Protein Response
01:30Other Stress Responses in Bacteria