PINK1/Parkin mediated mitophagy ameliorates palmitic acid-induced apoptosis through reducing mitochondrial ROS production in podocytes

Jiang, Xu-shun; Chen, Xuemei; Hua, Wei; He, Jian; Liu, Ting; Li, Xunjia; Wan, Jiang-min; Gan, Hua; Du, Xuqin

doi:10.1016/j.bbrc.2020.02.170

Cited by 50 publications

(38 citation statements)

References 31 publications

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“…Mitochondria also play important roles in oxidative stress and crosstalk in endoplasmic reticulum (ER) stress, the inflammasome, and autophagy in type 2 diabetes (Rocha et al 2020). A previous study indicated that palmitic acid induced excessive mitochondrial reactive oxygen species (ROS) accumulation in podocytes (Jiang et al 2020). Excessive mitochondrial ROS levels were associated with mitochondrial injury in mice with diabetic nephropathy (Hwang et al 2012).…”

Section: Introductionmentioning

confidence: 99%

The Kidney-Related Effects of Polystyrene Microplastics on Human Kidney Proximal Tubular Epithelial Cells HK-2 and Male C57BL/6 Mice

Wang

Lee

Hsu

et al. 2021

Environ Health Perspect

165

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BACKGROUND: Understanding the epidemic of chronic kidney disease of uncertain etiology may be critical for health policies and public health responses. Recent studies have shown that microplastics (MPs) contaminate our food chain and accumulate in the gut, liver, kidney, muscle, and so on. Humans manufacture many plastics-related products. Previous studies have indicated that particles of these products have several effects on the gut and liver. Polystyrene (PS)-MPs (PS-MPs) induce several responses, such as oxidative stress, and affect living organisms. OBJECTIVES: The aim of this study was to investigate the effects of PS-MPs in kidney cells in vitro and in vivo. METHODS: PS-MPs were evaluated in human kidney proximal tubular epithelial cells (HK-2 cells) and male C57BL/6 mice. Mitochondrial reactive oxygen species (ROS), endoplasmic reticulum (ER) stress, inflammation, and autophagy were analyzed in kidney cells. In vivo, we evaluated biomarkers of kidney function, kidney ultrastructure, muscle mass, and grip strength, and urine protein levels, as well as the accumulation of PS-MPs in the kidney tissue. RESULTS: Uptake of PS-MPs at different concentrations by HK-2 cells resulted in higher levels of mitochondrial ROS and the mitochondrial protein Bad. Cells exposed to PS-MPs had higher ER stress and markers of inflammation. MitoTEMPO, which is a mitochondrial ROS antioxidant, mitigated the higher levels of mitochondrial ROS, Bad, ER stress, and specific autophagy-related proteins seen with PS-MP exposure. Furthermore, cells exposed to PS-MPs had higher protein levels of LC3 and Beclin 1. PS-MPs also had changes in phosphorylation of mitogen-activated protein kinase (MAPK) and protein kinase B (AKT)/mitogen-activated protein kinase (mTOR) signaling pathways. In an in vivo study, PS-MPs accumulated and the treated mice had more histopathological lesions in the kidneys and higher levels of ER stress, inflammatory markers, and autophagy-related proteins in the kidneys after PS-MPs treatment by oral gavage. CONCLUSIONS:The results suggest that PS-MPs caused mitochondrial dysfunction, ER stress, inflammation, and autophagy in kidney cells and accumulated in HK-2 cells and in the kidneys of mice. These results suggest that long-term PS-MPs exposure may be a risk factor for kidney health.

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Section: Introductionmentioning

confidence: 99%

The Kidney-Related Effects of Polystyrene Microplastics on Human Kidney Proximal Tubular Epithelial Cells HK-2 and Male C57BL/6 Mice

Wang

Lee

Hsu

et al. 2021

Environ Health Perspect

165

View full text Add to dashboard Cite

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“…Other studies have confirmed the protective role of PINK1/parkin mitophagy in kidney diseases. PINK1/parkin signaling were found to decrease mitochondrial ROS (mtROS) and inflammasome activation in renal tubular epithelial cells [ 27 ], and to ameliorate fatty acid-induced apoptosis in diabetic kidney disease [ 28 ]. Similarly, a genetic study have demonstrated that overexpression of forkhead box class O1 (FOXO1) in rat kidney cortex, which enhanced PINK1/Parkin mitophagy, provided protective effect against high glucose-induced kidney injury [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

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

Yoon

Yoon³

et al. 2021

Cells

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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.

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“…In this context, the unhydrolyzed PINK1 protein attaches to the outer mitochondrial membrane and activates the autophagy process to eliminate the dysfunctional mitochondria. [36][37][38] Autophagy is also associated with cell migration, proliferation, and apoptosis, although the molecular mechanisms underlying the relationship between autophagy and cellular activities remain unclear. [39][40][41] The present study revealed that autophagy was severely suppressed in cells with stable interference of PINK1 expression ( Figure 4B-E), which suggests that deficient autophagy might be related to the PINK1 mediation of suppression of cell proliferation and migration.…”

Section: Discussionmentioning

confidence: 99%

<p><em>PINK1</em> Overexpression Promotes Cell Migration and Proliferation via Regulation of Autophagy and Predicts a Poor Prognosis in Lung Cancer Cases</p>

Xiao¹,

Liu²,

Zhang³

et al. 2020

CMAR

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Background: Lung cancer remains the leading cause of cancer-related death worldwide. The human PINK1 gene (PTEN induced kinase 1, Park6), an important gene for Parkinson's disease, was found to be associated with tumor development although the molecular mechanisms underlying this relationship remain largely unknown. Objective: To analyze the clinical value and molecular mechanism of PINK1 in non-small cell lung cancer (NSCLC). Materials and Methods: Western blot, qRT-PCR and Immunohistochemistry were employed to determine the levels of PINK1 in 87 paired NSCLC tissues, Oncomine and TCGA databases were also used for the evaluation of expression and prognosis of PINK1. The mitophagy, proliferation, migration, invasion, and apoptosis abilities of A549 and H1975 cells were detected, and the autophagy-related proteins in the cells were also determined. Results: Immunohistochemical staining revealed higher PINK1 expression in tumor tissues, which was strongly linked to the tumor-node-metastasis classification. Survival analysis of 1085 NSCLC patients also revealed that low PINK1 expression levels were associated with significantly longer overall survival. Univariate and multivariate analyses indicated that PINK1 expression was an independent predictor of overall survival among patients with NSCLC. We also evaluated the influence of PINK1 deficiency in NSCLC cell lines (A549 and H1975), which revealed significant suppression of migration capability and cell viability, as well as a significantly elevated apoptosis ratio. In cells with stable interference of PINK1 expression, dysfunctional mitochondria accumulated while autophagy was inhibited, which indicated that cell activity suppression was mediated by the accumulation of dysfunctional mitochondria. The suppression of migration and autophagy was reversed in cells that overexpressed PINK1. Conclusion: Our results suggest that PINK1 may be a potential therapeutic target and prognostic biomarker in NSCLC.

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PINK1/Parkin mediated mitophagy ameliorates palmitic acid-induced apoptosis through reducing mitochondrial ROS production in podocytes

Cited by 50 publications

References 31 publications

The Kidney-Related Effects of Polystyrene Microplastics on Human Kidney Proximal Tubular Epithelial Cells HK-2 and Male C57BL/6 Mice

The Kidney-Related Effects of Polystyrene Microplastics on Human Kidney Proximal Tubular Epithelial Cells HK-2 and Male C57BL/6 Mice

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

<p><em>PINK1</em> Overexpression Promotes Cell Migration and Proliferation via Regulation of Autophagy and Predicts a Poor Prognosis in Lung Cancer Cases</p>

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