Role of mitochondrial dysfunction and PINK1/Parkin-mediated mitophagy in Cd-induced hepatic lipid accumulation in chicken embryos.

Abstract

The present study was performed to investigate the effects of Cd exposure on lipid metabolism and mitochondrial dysfunction and to explore the role of mitophagy in Cd-induced dysregulation of lipid metabolism in chicken embryo liver tissues and hepatocytes. To this end, seven-day-old chicken embryos were exposed to different concentrations of Cd for 7 days, and primary chicken embryo hepatocytes were treated with Cd at four different concentrations for 6 h. Furthermore, the mitophagy inhibitor cyclosporine A (CsA) was used to investigate the role of mitophagy in Cd-induced disruption of lipid metabolism. Lipid accumulation, the expression levels of genes involved in lipid metabolism, mitochondrial dysfunction, and mitophagy were measured. The results demonstrated that Cd exposure increases hepatic triglyceride (TG) accumulation and the expression levels of lipogenic genes while decreasing those of lipolytic genes. Furthermore, Cd exposure was observed to alter mitochondrial morphology in terms of reduced size, excessive mitochondrial damage, and the formation of mitophagosomes. The co-localization of lysosome-associated membrane glycoprotein 2 and LC3 puncta was significantly increased in primary chicken embryo hepatocytes after Cd exposure. Moreover, Cd exposure increased LC3, PINK1, and Parkin protein expression levels. CsA effectively alleviated Cd-induced mitochondrial dysfunction, blocked mitochondrial membrane potential collapse, and suppressed PINK1/Parkin-mediated mitophagy. Furthermore, CsA treatment reversed the Cd-induced TG accumulation in liver tissues but further increased it in hepatocytes. Taken together, our findings demonstrate (for the first time) the importance of mitochondrial dysfunction and mitophagy via the PINK1/Parkin pathway in Cd-induced disruption of lipid metabolism.

• Authors: Dawei Chen, Di Ran, Chao Wang, Yinyin Liu, Yonggang Ma, Ruilong Song, Yushi Gao, Zongping Liu
• Journal: Life sciences (Life Sci) Vol. 284 Pg. 119906 (Nov 01 2021) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 34478761 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• Cadmium
• Cyclosporine
• Ubiquitin-Protein Ligases
• parkin protein
• Protein Kinases
• PTEN-induced putative kinase

Topics

• Animals
• Cadmium (toxicity)
• Chick Embryo
• Cyclosporine (pharmacology)
• Hepatocytes (drug effects, metabolism, ultrastructure)
• Lipid Metabolism (drug effects)
• Liver (drug effects, embryology, metabolism)
• Mitochondria, Liver (drug effects, pathology, ultrastructure)
• Mitophagy (drug effects)
• Models, Biological
• Protein Kinases (metabolism)
• Ubiquitin-Protein Ligases (metabolism)