RIPK1-mediated induction of mitophagy compromises the viability of extracellular-matrix-detached cells

Hawk, Mark A.; Gorsuch, Cassandra L.; Fagan, Patrick; Lee, Chan; Kim, Sung Eun; Hamann, Jens C.; Mason, Joshua; Weigel, Kelsey; Tsegaye, Matyas Abel; Shen, Luqun; Shuff, Sydney; Zuo, Junjun; Hu, Stephan; Jiang, Lei; Chapman, Sarah E.; Leevy, W. Matthew; DeBerardinis, Ralph J.; Overholtzer, Michael; Schafer, Zachary T.

doi:10.1038/s41556-018-0034-2

Cited by 75 publications

(50 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Because PGAM5 is closely related to PINK1 and Parkinson's disease (Imai et al , ; Sekine et al , ; Lu et al , ; Hawk et al , ), we examined whether PGAM5 and Stx17 are involved in PINK1/Parkin‐dependent mitophagy. To this end, we treated GFP‐Parkin‐expressing HeLa cells with CCCP.…”

Section: Resultsmentioning

confidence: 99%

“…PGAM5 is a member of the phosphoglycerate mutase family, but exhibits protein phosphatase activity toward Ser/Thr (Takeda et al , ) and His (Panda et al , ). Recent studies highlighted the importance of PGAM5 in a variety of cellular processes, including mitochondrial dynamics (Wilkins et al , ; Lavie et al , ; O'Mealey et al , ), mitophagy (Chen et al , ; Wu et al , ; Hawk et al , ), programmed cell death (Wang et al , ; Lin et al , ; Zhuang et al , ; Xu et al , ; He et al , ), the WNT/β‐catenin pathway (Rauschenberger et al , ; Bernkopf et al , ), immune responses (Kang et al , ; Moriwaki et al , ), and longevity (Borch Jensen et al , ). Several lines of evidence suggest the close relationship of PGAM5 with Parkinson's disease.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Syntaxin 17 regulates the localization and function of PGAM5 in mitochondrial division and mitophagy

et al. 2018

View full text Add to dashboard Cite

PGAM5, a mitochondrial protein phosphatase that is genetically and biochemically linked to PINK1, facilitates mitochondrial division by dephosphorylating the mitochondrial fission factor Drp1. At the onset of mitophagy, PGAM5 is cleaved by PARL, a rhomboid protease that degrades PINK1 in healthy cells, and the cleaved form facilitates the engulfment of damaged mitochondria by autophagosomes by dephosphorylating the mitophagy receptor FUNDC1. Here, we show that the function and localization of PGAM5 are regulated by syntaxin 17 (Stx17), a mitochondria-associated membrane/mitochondria protein implicated in mitochondrial dynamics in fed cells and autophagy in starved cells. In healthy cells, loss of Stx17 causes PGAM5 aggregation within mitochondria and thereby failure of the dephosphorylation of Drp1, leading to mitochondrial elongation. In Parkin-mediated mitophagy, Stx17 is prerequisite for PGAM5 to interact with FUNDC1. Our results reveal that the Stx17-PGAM5 axis plays pivotal roles in mitochondrial division and PINK1/Parkin-mediated mitophagy.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Syntaxin 17 regulates the localization and function of PGAM5 in mitochondrial division and mitophagy

et al. 2018

View full text Add to dashboard Cite

show abstract

“…We found that cholangiocarcinoma cells with differential RMP expression did not show differences in proliferation or migration under 2D culture conditions in vitro , although RMP overexpression promoted an increase in the colony formation capacity in a soft agar 3D environment of stimulation. After epithelial cells detach from the basement membrane, anoikis tends to occur, and some cells can continue to resist this apoptosis, showing anchorage‐independent growth . It has been reported that cells must surmount different kinds of stress, including increased ROS levels, to maintain anchorage‐independent growth .…”

Section: Discussionmentioning

confidence: 99%

RPB5‐Mediating Protein Promotes Cholangiocarcinoma Tumorigenesis and Drug Resistance by Competing With NRF2 for KEAP1 Binding

et al. 2020

View full text Add to dashboard Cite

BaCKgRoUND aND aIMS:Cancer cell survival depends on the balance between reactive oxygen species production and scavenging, which is regulated primarily by NRF2 during tumorigenesis. Here, we demonstrate that deletion of RBP5mediating protein (RMP) in an autonomous mouse model of intrahepatic cholangiocarcinoma (ICC) delays tumor progression. appRoaCH aND ReSUltS: RMP-overexpressing tumor cells exhibited enhanced tolerance to oxidative stress and apoptosis. Mechanistically, RMP competes with NRF2 for binding to the Kelch domain of KEAP1 (Kelch-like ECH-associated protein 1) through the E**E motif, leading to decreased NRF2 degradation via ubiquitination, thus increasing NRF2 nuclear translocation and downstream transactivation of antioxidant genes. This RMP-KEAP1-NRF2 axis promotes ICC tumorigenesis, metastasis, and drug resistance. Consistent with these findings, the RMP level in human ICC is positively correlated with the protein level of NRF2 and is associated with poor prognosis.CoNClUSIoN: These findings reveal that RMP is involved in the oxidative stress defense program and could be exploited for targeted cancer therapies. (Hepatology 2020;71:2005-2022.

show abstract

“…The process of mitophagy plays multimodal roles in the survival of cells. Benign mitophagy renders the cell adaptive to certain levels of stress, but under lasting or overwhelming stress, abnormal mitophagy takes place and compromises the cells viability [113,114]. Mitochondria play a pivotal role in the energy acquisition of eukaryotes and too great a loss of the crucial organelle destroys the energy metabolism of an organism.…”

Section: Discussionmentioning

confidence: 99%

Cuminal Inhibits Trichothecium roseum Growth by Triggering Cell Starvation: Transcriptome and Proteome Analysis

Zhang

et al. 2020

Microorganisms

View full text Add to dashboard Cite

Trichothecium roseum is a harmful postharvest fungus causing serious damage, together with the secretion of insidious mycotoxins, on apples, melons, and other important fruits. Cuminal, a predominant component of Cuminum cyminum essential oil has proven to successfully inhibit the growth of T. roseum in vitro and in vivo. Electron microscopic observations revealed cuminal exposure impaired the fungal morphology and ultrastructure, particularly the plasmalemma. Transcriptome and proteome analysis was used to investigate the responses of T. roseum to exposure of cuminal. In total, 2825 differentially expressed transcripts (1516 up and 1309 down) and 225 differentially expressed proteins (90 up and 135 down) were determined. Overall, notable parts of these differentially expressed genes functionally belong to subcellular localities of the membrane system and cytosol, along with ribosomes, mitochondria and peroxisomes. According to the localization analysis and the biological annotation of these genes, carbohydrate and lipids metabolism, redox homeostasis, and asexual reproduction were among the most enriched gene ontology (GO) terms. Biological pathway enrichment analysis showed that lipids and amino acid degradation, ATP-binding cassette transporters, membrane reconstitution, mRNA surveillance pathway and peroxisome were elevated, whereas secondary metabolite biosynthesis, cell cycle, and glycolysis/gluconeogenesis were down regulated. Further integrated omics analysis showed that cuminal exposure first impaired the polarity of the cytoplasmic membrane and then triggered the reconstitution and dysfunction of fungal plasmalemma, resulting in handicapped nutrient procurement of the cells. Consequently, fungal cells showed starvation stress with limited carbohydrate metabolism, resulting a metabolic shift to catabolism of the cell's own components in response to the stress. Additionally, these predicaments brought about oxidative stress, which, in collaboration with the starvation, damaged certain critical organelles such as mitochondria. Such degeneration, accompanied by energy deficiency, suppressed the biosynthesis of essential proteins and inhibited fungal growth.fungicides to be used for postharvest treatment, reduced efficacy due to the emergence of pathogen resistance to these chemicals, and the growing public concerns over chemical residues in food and the environment have necessitated the seeking of alternative solutions to control the fungal spoilage and to guarantee food safety and consumer health [8].Essential oils (EOs), generally recognized as safe by the US Food and Drug Administration [9], are natural substances with established antimicrobial activities [10,11] and are a candidate instrument for controlling postharvest disease [12,13]. Nonetheless, this candidacy is compromised by the expensiveness of these natural substances due to their generally low yields. However, exploring their mode of actions is valuable to the development of novel alternatives.The multicomponent EOs attribute their mode of act...

show abstract

RIPK1-mediated induction of mitophagy compromises the viability of extracellular-matrix-detached cells

Cited by 75 publications

References 56 publications

Syntaxin 17 regulates the localization and function of PGAM5 in mitochondrial division and mitophagy

Syntaxin 17 regulates the localization and function of PGAM5 in mitochondrial division and mitophagy

RPB5‐Mediating Protein Promotes Cholangiocarcinoma Tumorigenesis and Drug Resistance by Competing With NRF2 for KEAP1 Binding

Cuminal Inhibits Trichothecium roseum Growth by Triggering Cell Starvation: Transcriptome and Proteome Analysis

Contact Info

Product

Resources

About