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Human antigen R regulates hypoxia‐induced mitophagy in renal tubular cells through PARKIN/BNIP3L expressions
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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933924/ https://www.ncbi.nlm.nih.gov/pubmed/33496385 http://dx.doi.org/10.1111/jcmm.16301 |
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author | Yu, Shao‐Hua Palanisamy, Kalaiselvi Sun, Kuo‐Ting Li, Xin Wang, Yao‐Ming Lin, Feng‐Yen Chen, Kuen‐Bao Wang, I‐Kuan Yu, Tung‐Min Li, Chi‐Yuan |
author_facet | Yu, Shao‐Hua Palanisamy, Kalaiselvi Sun, Kuo‐Ting Li, Xin Wang, Yao‐Ming Lin, Feng‐Yen Chen, Kuen‐Bao Wang, I‐Kuan Yu, Tung‐Min Li, Chi‐Yuan |
author_sort | Yu, Shao‐Hua |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7933924 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-79339242021-03-15 Human antigen R regulates hypoxia‐induced mitophagy in renal tubular cells through PARKIN/BNIP3L expressions Yu, Shao‐Hua Palanisamy, Kalaiselvi Sun, Kuo‐Ting Li, Xin Wang, Yao‐Ming Lin, Feng‐Yen Chen, Kuen‐Bao Wang, I‐Kuan Yu, Tung‐Min Li, Chi‐Yuan J Cell Mol Med Original Articles 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. John Wiley and Sons Inc. 2021-01-26 2021-03 /pmc/articles/PMC7933924/ /pubmed/33496385 http://dx.doi.org/10.1111/jcmm.16301 Text en © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Yu, Shao‐Hua Palanisamy, Kalaiselvi Sun, Kuo‐Ting Li, Xin Wang, Yao‐Ming Lin, Feng‐Yen Chen, Kuen‐Bao Wang, I‐Kuan Yu, Tung‐Min Li, Chi‐Yuan Human antigen R regulates hypoxia‐induced mitophagy in renal tubular cells through PARKIN/BNIP3L expressions |
title | Human antigen R regulates hypoxia‐induced mitophagy in renal tubular cells through PARKIN/BNIP3L expressions |
title_full | Human antigen R regulates hypoxia‐induced mitophagy in renal tubular cells through PARKIN/BNIP3L expressions |
title_fullStr | Human antigen R regulates hypoxia‐induced mitophagy in renal tubular cells through PARKIN/BNIP3L expressions |
title_full_unstemmed | Human antigen R regulates hypoxia‐induced mitophagy in renal tubular cells through PARKIN/BNIP3L expressions |
title_short | Human antigen R regulates hypoxia‐induced mitophagy in renal tubular cells through PARKIN/BNIP3L expressions |
title_sort | human antigen r regulates hypoxia‐induced mitophagy in renal tubular cells through parkin/bnip3l expressions |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933924/ https://www.ncbi.nlm.nih.gov/pubmed/33496385 http://dx.doi.org/10.1111/jcmm.16301 |
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