Sestrin-2 and BNIP3 regulate autophagy and mitophagy in renal tubular cells in acute kidney injury

May 24, 2013American journal of physiology. Renal physiology

Sestrin-2 and BNIP3 control cell recycling and damaged mitochondria removal in kidney cells during acute injury

AI simplified

Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Renal ischemia-reperfusion injury upregulated the expression of BNIP3 and sestrin-2 in the proximal tubules.

BNIP3 and sestrin-2 are regulated by hypoxia-inducible factor (HIF)-1α and p53, respectively.
Hypoxia increased BNIP3 mRNA and protein levels in renal tubular cells in a HIF-1α-dependent manner.
Oxidative stress led to upregulation of sestrin-2 mRNA and protein through a p53-dependent mechanism.
Overexpression of BNIP3 or sestrin-2 induced autophagy markers and autophagosome formation in renal tubular cells.
BNIP3-induced autophagosomes were predominantly located at the mitochondria, indicating a role in mitophagy.

AI simplified

Autophagy is a cellular recycling process induced in response to many types of stress. However, little is known of the signaling pathways that regulate autophagy during acute kidney injury (AKI). Bcl-2/adenovirus E1B 19 kDa-interacting protein (BNIP)3 and sestrin-2 are the target proteins of hypoxia-inducible factor (HIF)-1α and p53, respectively. The aim of this study was to investigate the roles of BNIP3 and sestrin-2 in oxidative stress-induced autophagy during AKI. We used rat ischemia-reperfusion injury and cultured renal tubular (NRK-52E) cells as in vivo and in vitro models of AKI, respectively. Renal ischemia-reperfusion injury upregulated the expression of BNIP3 and sestrin-2 in the proximal tubules, as measured by immunohistochemical staining and Western blot analysis. In vitro, NRK-52E cells exposed to hypoxia showed increased expression of BNIP3 mRNA and protein in a HIF-1α-dependent manner. In contrast, sestrin-2 mRNA and protein expression were upregulated in a p53-dependent manner after exposure to oxidative stress (exogenous H2O2). NRK-52E cells stably transfected with a fusion protein between green fluorescent protein and light chain 3 were used to investigate autophagy. Overexpression of BNIP3 or sestrin-2 in these cells induced light chain 3 expression and formation of autophagosomes. Interestingly, BNIP3-induced autophagosomes were mainly localized to the mitochondria, suggesting that this protein selectively induces mitophagy. These observations demonstrate that autophagy is induced in renal tubules by at least two independent pathways involving p53-sestrin-2 and HIF-1α-BNIP3, which may be activated by different types of stress to protect the renal tubules during AKI.

Full Text

Full text is available at the source.

View full text ↗

Sestrin-2 and BNIP3 regulate autophagy and mitophagy in renal tubular cells in acute kidney injury

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief