Human antigen R regulates hypoxia-induced mitophagy in renal tubular cells through PARKIN/BNIP3L expressions.

Abstract

Mitochondrial dysfunction contributes to the pathophysiology of acute kidney injury (AKI). Mitophagy selectively degrades damaged mitochondria and thereby regulates cellular homeostasis. RNA-binding proteins (RBPs) regulate RNA processing at multiple levels and thereby control cellular function. In this study, we aimed to understand the role of human antigen R (HuR) in hypoxia-induced mitophagy process in the renal tubular cells. Mitophagy marker expressions (PARKIN, p-PARKIN, PINK1, BNIP3L, BNIP3, LC3) were determined by western blot analysis. Immunofluorescence studies were performed to analyze mitophagosome, mitolysosome, co-localization of p-PARKIN/TOMM20 and BNIP3L/TOMM20. HuR-mediated regulation of PARKIN/BNIP3L expressions was determined by RNA-immunoprecipitation analysis and RNA stability experiments. Hypoxia induced mitochondrial dysfunction by increased ROS, decline in membrane potential and activated mitophagy through up-regulated PARKIN, PINK1, BNIP3 and BNIP3L expressions. HuR knockdown studies revealed that HuR regulates hypoxia-induced mitophagosome and mitolysosome formation. HuR was significantly bound to PARKIN and BNIP3L mRNA under hypoxia and thereby up-regulated their expressions through mRNA stability. Altogether, our data highlight the importance of HuR in mitophagy regulation through up-regulating PARKIN/BNIP3L expressions in renal tubular cells.

• Authors: Shao-Hua Yu, Kalaiselvi Palanisamy, Kuo-Ting Sun, Xin Li, Yao-Ming Wang, Feng-Yen Lin, Kuen-Bao Chen, I-Kuan Wang, Tung-Min Yu, Chi-Yuan Li
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 25 Issue 5 Pg. 2691-2702 (03 2021) ISSN: 1582-4934 [Electronic] England
• PMID: 33496385 (Publication Type: Journal Article)
• Copyright: © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Chemical References

• BNIP3L protein, human
• ELAV-Like Protein 1
• Membrane Proteins
• Proto-Oncogene Proteins
• Tumor Suppressor Proteins
• Ubiquitin-Protein Ligases
• parkin protein

Topics

• Acute Kidney Injury (etiology, metabolism, pathology)
• Cell Line, Tumor
• ELAV-Like Protein 1 (metabolism)
• Epithelial Cells (metabolism)
• Gene Expression
• Gene Knockdown Techniques
• Humans
• Hypoxia (genetics, metabolism)
• Kidney Tubules
• Lysosomes (metabolism)
• Membrane Proteins (genetics)
• Mitochondria (genetics, metabolism)
• Mitophagy (genetics)
• Models, Biological
• Phagosomes (metabolism)
• Proto-Oncogene Proteins (genetics)
• Tumor Suppressor Proteins (genetics)
• Ubiquitin-Protein Ligases (genetics)