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

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

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)2691-2702
Number of pages12
JournalJournal of Cellular and Molecular Medicine
Volume25
Issue number5
DOIs
Publication statusPublished - Mar 2021

Keywords

  • acute kidney injury
  • BNIP3L
  • HK-2
  • HuR
  • mitophagy
  • PARKIN

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

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