Mitophagy: Basic Mechanism and Potential Role in Kidney Diseases

Tang, Chengyuan; He, Liyu; Liu, Jing; Dong, Zheng

doi:10.1159/000381510

Cited by 39 publications

(32 citation statements)

References 101 publications

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“…35 Despite these observations, the main pathway of mitophagy that is responsible for mitochondrial quality control in kidneys remains unclear and the role of mitophagy in the pathogenesis of renal diseases remains to be elucidated. 36 In the present study, we have demonstrated mitophagy induction in proximal tubular cells during renal I-R, which is suppressed in Pink1-and Park2-deficient mice. Notably, Pink1 and Park2 deficiency aggravate renal I-Rinduced kidney injury, and enhance mitochondrial damage, ROS production, tubular cell apoptosis and tubulointerstitial inflammation.…”

Section: Introductionsupporting

confidence: 58%

PINK1-PRKN/PARK2 pathway of mitophagy is activated to protect against renal ischemia-reperfusion injury

et al. 2018

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Damaged or dysfunctional mitochondria are toxic to the cell by producing reactive oxygen species and releasing cell death factors. Therefore, timely removal of these organelles is critical to cellular homeostasis and viability. Mitophagy is the mechanism of selective degradation of mitochondria via autophagy. The significance of mitophagy in kidney diseases, including ischemic acute kidney injury (AKI), has yet to be established, and the involved pathway of mitophagy remains poorly understood. Here, we show that mitophagy is induced in renal proximal tubular cells in both in vitro and in vivo models of ischemic AKI. Mitophagy under these conditions is abrogated by Pink1 and Park2 deficiency, supporting a critical role of the PINK1-PARK2 pathway in tubular cell mitophagy. Moreover, ischemic AKI is aggravated in pink1 andpark2 single- as well as double-knockout mice. Mechanistically, Pink1 and Park2 deficiency enhances mitochondrial damage, reactive oxygen species production, and inflammatory response. Taken together, these results indicate that PINK1-PARK2-mediated mitophagy plays an important role in mitochondrial quality control, tubular cell survival, and renal function during AKI.

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Section: Introductionsupporting

confidence: 58%

PINK1-PRKN/PARK2 pathway of mitophagy is activated to protect against renal ischemia-reperfusion injury

et al. 2018

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“…BNIP3 and NIX are also apoptotic regulators that can induce cell death or autophagy by increasing the production of ROS, by binding to pro-apoptotic proteins of the BCL-2 family, or by inhibiting the GTP-binding protein RHEB, an upstream activator of mTOR 131–133 . Previous studies suggest that crosstalk exists between both of the mechanisms that can regulate mitophagy 127,134,135 , although the mechanisms of this proposed crosstalk are unclear and additional studies are needed to determine the mechanisms that regulate mitophagy in renal disease.…”

Section: Maintaining Mitochondrial Homeostasismentioning

confidence: 99%

Mitochondrial energetics in the kidney

2017

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The kidney requires a large number of mitochondria to remove waste from the blood and regulate fluid and electrolyte balance. Mitochondria provide the energy to drive these important functions and can adapt to different metabolic conditions through a number of signalling pathways (for example, mechanistic target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) pathways) that activate the transcriptional co-activator peroxisome proliferator-activated receptor-γ co-activator 1α (PGC1α), and by balancing mitochondrial dynamics and energetics to maintain mitochondrial homeostasis. Mitochondrial dysfunction leads to a decrease in ATP production, alterations in cellular functions and structure, and the loss of renal function. Persistent mitochondrial dysfunction has a role in the early stages and progression of renal diseases, such as acute kidney injury (AKI) and diabetic nephropathy, as it disrupts mitochondrial homeostasis and thus normal kidney function. Improving mitochondrial homeostasis and function has the potential to restore renal function, and administering compounds that stimulate mitochondrial biogenesis can restore mitochondrial and renal function in mouse models of AKI and diabetes mellitus. Furthermore, inhibiting the fission protein dynamin 1-like protein (DRP1) might ameliorate ischaemic renal injury by blocking mitochondrial fission.

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“…Proper mitophagy is not only a prerequisite for cell survival but also plays a crucial role under pathological pressures, including hepatic diseases, angiocardiopathy, and neurodegeneration (Dai et al, 2010;Lionaki, Markaki, Palikaras, & Tavernarakis, 2015;Tang, He, Liu, & Dong, 2015). Mitophagy can be both beneficial and harmful under certain pathophysiological conditions (Palikaras, Daskalaki, Markaki, & Tavernarakis, 2017).…”

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confidence: 99%

Activation of mitophagy in inflamed odontoblasts

Yang

Duan

et al. 2019

Oral Diseases

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Objectives Mitophagy is an important mitochondrial quality control mechanism. In this study, we investigated the mitochondrial damage and mitophagy occurred in inflammatory human dental pulp and lipopolysaccharide‐stimulated preodontoblasts. Materials and Methods In dental pulp tissues and lipopolysaccharide‐stimulated preodontoblasts, immunofluorescences and Western blot were performed to detect the expression of mitochondrial and mitophagy‐related proteins, and autophagy markers were also examined. Reactive oxygen species generated by mitochondria were examined by MitoSOX. Transmission electron microscope (TEM) was used to examine the morphology of mitochondria in lipopolysaccharide‐stimulated preodontoblasts. Results The active fission activity of mitochondria and mitophagy in inflammatory dental pulp was observed. In lipopolysaccharide‐treated preodontoblasts, mitophagy‐related proteins were also upregulated. Moreover, increased reactive oxygen species in the inflamed preodontoblasts were observed. Additionally, single‐membrane autolysosomes containing partially degraded mitochondria with swollen inner membranes in lipopolysaccharide‐treated preodontoblasts were observed by TEM. Conclusions These results indicate that mitochondria were damaged and mitophagy might be activated to degrade impaired mitochondria in inflamed odontoblasts.

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Mitophagy: Basic Mechanism and Potential Role in Kidney Diseases

Cited by 39 publications

References 101 publications

PINK1-PRKN/PARK2 pathway of mitophagy is activated to protect against renal ischemia-reperfusion injury

PINK1-PRKN/PARK2 pathway of mitophagy is activated to protect against renal ischemia-reperfusion injury

Mitochondrial energetics in the kidney

Activation of mitophagy in inflamed odontoblasts

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