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Melatonin Treatment Improves Renal Fibrosis via miR-4516/SIAH3/PINK1 Axis.

ABSTRACT: Dysregulation in mitophagy, in addition to contributing to imbalance in the mitochondrial dynamic, has been implicated in the development of renal fibrosis and progression of chronic kidney disease (CKD). However, the current understanding of the precise mechanisms behind the pathogenic loss of mitophagy remains unclear for developing cures for CKD. We found that miR-4516 is downregulated and its target SIAH3, an E3 ubiquitin protein ligase that reduces PINK1 accumulation to damaged mitochondria, is upregulated in the renal cortex of CKD mice. Here, we demonstrated that melatonin injection induces miR-4516 expression and suppresses SIAH3, and promotes PINK1/Parkin-mediated mitophagy. Furthermore, we demonstrated that melatonin injection attenuates the pathological features of CKD by improving mitochondrial homeostasis. Our data supports that mitochondrial autophagy regulation by activating miR-4516/SIAH3/PINK1 mitophagy signaling axis can be a viable new strategy for treating CKD.

SUBMITTER: Yoon YM

PROVIDER: S-EPMC8307213 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Melatonin Treatment Improves Renal Fibrosis via miR-4516/SIAH3/PINK1 Axis.

Yoon Yeo Min YM Go Gyeongyun G Yoon Sungtae S Lim Ji Ho JH Lee Gaeun G Lee Jun Hee JH Lee Sang Hun SH

Cells 20210703 7

Dysregulation in mitophagy, in addition to contributing to imbalance in the mitochondrial dynamic, has been implicated in the development of renal fibrosis and progression of chronic kidney disease (CKD). However, the current understanding of the precise mechanisms behind the pathogenic loss of mitophagy remains unclear for developing cures for CKD. We found that miR-4516 is downregulated and its target SIAH3, an E3 ubiquitin protein ligase that reduces PINK1 accumulation to damaged mitochondria ...[more]

PMID: 34359852

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