Drp1-regulated PARK2-dependent mitophagy protects against renal fibrosis in unilateral ureteral obstruction

Li, Shu; Lin, Qisheng; Shao, Xinghua; Zhu, Xuying; Wu, Jinlong; Wu, Bei; Zhang, Minfang; Zhou, Wenyan; Zhou, Yijun; Jin, Haijiao; Zhang, Zhen; Chen, Qi; Shen, Jianxiao; Mou, Shan; Gu, Leyi; Ni, Zhaohui

doi:10.1016/j.freeradbiomed.2019.12.005

Cited by 82 publications

(65 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Compromised mitochondrial bioenergetics contribute to the development of TIF and CKD [3]. In line with our findings, others have shown that deficiency of mitophagy by Pink1 or Park2 gene deletion markedly increased mROS production and mitochondrial damage, which worsened renal fibrosis after UUO [16]. These effects were rescued by a mitochondria-targeted antioxidant.…”

Section: Tubulointerstitial Fibrosissupporting

confidence: 90%

“…Another investigational drug that targets the IMM is Bendavia, a tetrapeptide that suppressed the mitochondrial permeability transition pore (MPTP) and attenuated oxidative stress, tubular injury, and apoptosis in experimental models of IRI [91]. Mitochondrial division inhibitor 1 (Mdivi-1), an inhibitor of DRP1-mediated mitochondrial fission, partially ameliorated ischemia-induced kidney injury [35], but it worsened renal fibrosis induced by UUO, raising concerns about its use [16]. Szeto-Schiller (SS)-31 peptide (H-D-Arg-Dmt-Lys-Phe-NH2) is another mROS scavenger that selectively targets the IMM and binds cardiolipin [34].…”

Section: Mitochondria-targeted Therapeutic Approaches To Akimentioning

confidence: 99%

“…During cellular injury, the activation of mitochondrial fission and concurrent arrest of mitochondrial fusion are associated with recruitment of DRP1 to the OMM and B-cell lymphoma 2 (BCL2)-associated X protein (BAX)/ BCL2-antagonist/killer 1 (BAK)-mediated OMM permeabilization, which results in mitochondrial fragmentation and apoptosis [7]. Fragmented mitochondria can be removed through DRP1-regulated mitophagy to suppress cell death [16]. Mitochondrial fission thus promotes recycling of damaged mitochondria and protects healthy mitochondria from removal via mitophagy [17].…”

mentioning

confidence: 99%

See 2 more Smart Citations

Mitochondrial dysfunction in kidney injury, inflammation, and disease: Potential therapeutic approaches

Bhatia¹,

Capili²,

Choi

2020

Kidney Res Clin Pract

109

104

View full text Add to dashboard Cite

Renal inflammation and tissue damage during acute kidney injury (AKI) and chronic kidney disease (CKD) have been linked to mitochondrial structural and functional alterations [1,2]. Mitochondria are a highly complex interconnected network of organelles that fulfill cellular energy needs. The kidney, an organ with high energy demands, is rich in mitochondria. Mitochondrial dysfunction arising from disturbances in the regulation of the mitochondrial electron transport chain (ETC), proton gradient, and membrane potential results in reduced adenosine triphosphate (ATP) and increased production of mitochondrial-derived reactive oxygen species (mROS), which promotes kidney injury and inflammation [3,4].

show abstract

Section: Tubulointerstitial Fibrosissupporting

confidence: 90%

Section: Mitochondria-targeted Therapeutic Approaches To Akimentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Mitochondrial dysfunction in kidney injury, inflammation, and disease: Potential therapeutic approaches

Bhatia¹,

Capili²,

Choi

2020

Kidney Res Clin Pract

109

104

View full text Add to dashboard Cite

show abstract

“…A key regulator of mitochondrial fission is Drp1 -a member of the dynamin family of large GTPases (Labrousse et al, 1999). Although multiple reports have shown that Drp1 is required for both PINK1-dependent and independent mitophagy pathways (Lee et al, 2011;Kageyama et al, 2014;Wu et al, 2016;Li et al, 2019;Zachari et al, 2019), other studies suggest that it might be dispensable for mitophagy (Murakawa et al, 2015;Yamashita et al, 2016;Burman et al, 2017). Thus, mitophagy dependency on Drp1 could be potentially context specific and further investigation is needed to understand its role in this pathway.…”

Section: Recruitment Of the Autophagic Machinerymentioning

confidence: 99%

Mammalian Mitophagosome Formation: A Focus on the Early Signals and Steps

Zachari

Ktistakis

2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Mitophagy, a conserved intracellular process by which mitochondria are eliminated via the autophagic machinery, is a quality control mechanism which facilitates maintenance of a functional mitochondrial network and cell homeostasis, making it a key process in development and longevity. Mitophagy has been linked to multiple human disorders, especially neurodegenerative diseases where the long-lived neurons are relying on clearance of old/damaged mitochondria to survive. During the past decade, the availability of novel tools to study mitophagy both in vitro and in vivo has significantly advanced our understanding of the molecular mechanisms governing this fundamental process in normal physiology and in various disease models. We here give an overview of the known mitophagy pathways and how they are induced, with a particular emphasis on the early events governing mitophagosome formation.

show abstract

“…Studies have demonstrated that Drp-1 exerts its physiological function by mediating mitophagy [28]. Li et al reported that Drp-1 protected the renal tubular epithelial cell against unilateral ureteral obstruction by regulating PARK2-dependent mitophagy [29]. Zuo et al reported that Drp-1 mediates mitophagy via mitochondrial fission to protect against mitochondrial dysfunction in cerebral ischemia [30].…”

mentioning

confidence: 99%

Drp-1 as Potential Therapeutic Target for Lipopolysaccharide-Induced Vascular Hyperpermeability

Luo

Cai

et al. 2020

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Mitochondria-dependent apoptotic signaling has a critical role in the pathogenesis of vascular hyperpermeability (VH). Dynamin-related protein-1- (Drp-1-) mediated mitochondrial fission plays an important role in mitochondrial homeostasis. In the present study, we studied the involvement of Drp-1 in resistance to VH induced by lipopolysaccharide (LPS). To establish the model of LPS-induced VH, LPS at 15 mg/kg was injected into rats in vivo and rat pulmonary microvascular endothelial cells were exposed to 500 ng/ml LPS in vitro. We found that depletion of Drp-1 remarkedly exacerbated the mitochondria-dependent apoptosis induced by LPS, as evidenced by reduced apoptosis, mitochondrial membrane potential (MMP) depolarization, and activation of caspase-3 and caspase-9. Increased FITC-dextran flux indicated endothelial barrier disruption. In addition, overexpression of Drp-1 prevented LPS-induced endothelial hyperpermeability and upregulated mitophagy, as evidenced by the loss of mitochondrial mass and increased PINK1 expression and mitochondrial Parkin. However, the mitophagy inhibitor, 3-Methyladenine, blocked these protective effects of Drp-1. Furthermore, inhibition of Drp-1 using mitochondrial division inhibitor 1 markedly inhibited LPS-induced mitophagy and aggravated LPS-induced VH, as shown by increased FITC-dextran extravasation. These findings implied that Drp-1 strengthens resistance to mitochondria-dependent apoptosis by regulating mitophagy, suggesting Drp-1 as a possible therapeutic target in LPS-induced VH.

show abstract

Drp1-regulated PARK2-dependent mitophagy protects against renal fibrosis in unilateral ureteral obstruction

Cited by 82 publications

References 49 publications

Mitochondrial dysfunction in kidney injury, inflammation, and disease: Potential therapeutic approaches

Mitochondrial dysfunction in kidney injury, inflammation, and disease: Potential therapeutic approaches

Mammalian Mitophagosome Formation: A Focus on the Early Signals and Steps

Drp-1 as Potential Therapeutic Target for Lipopolysaccharide-Induced Vascular Hyperpermeability

Contact Info

Product

Resources

About