Autophagic degradation of the chloroplastic 2-phosphoglycolate phosphatase TaPGLP1 in wheat

AbstractDespite transcranial Direct Current Stimulation (DCS) is currently proposed as a symptomatic treatment in Parkinson’s disease, the intracellular and molecular mechanisms elicited by this technique are still unknown, and its disease-modifying potential unexplored. Aim of this study was to elucidate the on-line and off-line effects of DCS on the expression, aggregation and degradation of alpha-synuclein (asyn) in a human neuroblastoma cell line under basal conditions and in presence of pharmachologically-induced increased asyn levels. Following DCS, gene and protein expression of asyn and its main autophagic catabolic pathways were assessed by real-time PCR and Western blot, extracellular asyn levels by Dot blot. We found that, under standard conditions, DCS increased monomeric and reduced oligomeric asyn forms, with a concomitant down-regulation of both macroautophagy and chaperone-mediated autophagy. Differently, in presence of rotenone-induced increased asyn, DCS efficiently counteracted asyn accumulation, not acting on its gene transcription, but potentiating its degradation. DCS also reduced intracellular and extracellular asyn levels, increased following lysosomal inhibition, independently from autophagic degradation, suggesting that other mechanisms are also involved. Collectively, these findings suggest that DCS exerts on-line and off-line effects on the expression, aggregation and autophagic degradation of asyn, indicating a till unknown neuroprotective role of tDCS.

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RNF220-mediated ubiquitination promotes aggresomal accumulation and autophagic degradation of cytoplasmic Gli via HDAC6

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2021.03.156 ◽

2021 ◽

Vol 557 ◽

pp. 323-328

Author(s):

Huishan Wang ◽

Chencheng Yang ◽

Yuwei Li ◽

Shuhua Zhao ◽

Pengcheng Ma ◽

...

Keyword(s):

Autophagic Degradation

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The STING1 network regulates autophagy and cell death

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-021-00613-4 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Ruoxi Zhang ◽

Rui Kang ◽

Daolin Tang

Keyword(s):

Cell Death ◽

Mitotic Cell ◽

Therapeutic Interventions ◽

Type I Interferons ◽

Microbial Pathogens ◽

Type I ◽

Autophagic Degradation ◽

Health And Disease ◽

Shed Light ◽

Pro Inflammatory Cytokines

AbstractCell death and immune response are at the core of life. In past decades, the endoplasmic reticulum (ER) protein STING1 (also known as STING or TMEM173) was found to play a fundamental role in the production of type I interferons (IFNs) and pro-inflammatory cytokines in response to DNA derived from invading microbial pathogens or damaged hosts by activating multiple transcription factors. In addition to this well-known function in infection, inflammation, and immunity, emerging evidence suggests that the STING1-dependent signaling network is implicated in health and disease by regulating autophagic degradation or various cell death modalities (e.g., apoptosis, necroptosis, pyroptosis, ferroptosis, mitotic cell death, and immunogenic cell death [ICD]). Here, we outline the latest advances in our understanding of the regulating mechanisms and signaling pathways of STING1 in autophagy and cell death, which may shed light on new targets for therapeutic interventions.

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RIP3 impedes transcription factor EB to suppress autophagic degradation in septic acute kidney injury

Cell Death and Disease ◽

10.1038/s41419-021-03865-8 ◽

2021 ◽

Vol 12 (6) ◽

Author(s):

Ruizhao Li ◽

Xingchen Zhao ◽

Shu Zhang ◽

Wei Dong ◽

Li Zhang ◽

...

Keyword(s):

Acute Kidney Injury ◽

Transcription Factor ◽

Nuclear Translocation ◽

Kidney Injury ◽

Septic Acute Kidney Injury ◽

Transcription Factor Eb ◽

Autophagic Degradation ◽

Lps Treatment

AbstractAutophagy is an important renal-protective mechanism in septic acute kidney injury (AKI). Receptor interacting protein kinase 3 (RIP3) has been implicated in the renal tubular injury and renal dysfunction during septic AKI. Here we investigated the role and mechanism of RIP3 on autophagy in septic AKI. We showed an activation of RIP3, accompanied by an accumulation of the autophagosome marker LC3II and the autophagic substrate p62, in the kidneys of lipopolysaccharide (LPS)-induced septic AKI mice and LPS-treated cultured renal proximal tubular epithelial cells (PTECs). The lysosome inhibitor did not further increase the levels of LCII or p62 in LPS-treated PTECs. Moreover, inhibition of RIP3 attenuated the aberrant accumulation of LC3II and p62 under LPS treatment in vivo and in vitro. By utilizing mCherry-GFP-LC3 autophagy reporter mice in vivo and PTECs overexpression mRFP-GFP-LC3 in vitro, we observed that inhibition of RIP3 restored the formation of autolysosomes and eliminated the accumulated autophagosomes under LPS treatment. These results indicated that RIP3 impaired autophagic degradation, contributing to the accumulation of autophagosomes. Mechanistically, the nuclear translocation of transcription factor EB (TFEB), a master regulator of the lysosome and autophagy pathway, was inhibited in LPS-induced mice and LPS-treated PTECs. Inhibition of RIP3 restored the nuclear translocation of TFEB in vivo and in vitro. Co-immunoprecipitation further showed an interaction of RIP3 and TFEB in LPS-treated PTECs. Also, the expression of LAMP1 and cathepsin B, two potential target genes of TFEB involved in lysosome function, were decreased under LPS treatment in vivo and in vitro, and this decrease was rescued by inhibiting RIP3. Finally, overexpression of TFEB restored the autophagic degradation in LPS-treated PTECs. Together, the present study has identified a pivotal role of RIP3 in suppressing autophagic degradation through impeding the TFEB-lysosome pathway in septic AKI, providing potential therapeutic targets for the prevention and treatment of septic AKI.

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Phosphoglycolate Phosphatase in Several Population Groups in Israel

Human Heredity ◽

10.1159/000153184 ◽

1981 ◽

Vol 31 (2) ◽

pp. 89-92 ◽

Cited By ~ 4

Author(s):

R. Golan ◽

J.B. Ben-Ezzer ◽

A. Szeinberg

Keyword(s):

Population Groups ◽

Phosphoglycolate Phosphatase

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Phosphoglycolate has profound metabolic effects but most likely no role in a metabolic DNA response in cancer cell lines

Biochemical Journal ◽

10.1042/bcj20180435 ◽

2019 ◽

Vol 476 (4) ◽

pp. 629-643 ◽

Cited By ~ 1

Author(s):

Isabelle Gerin ◽

Marina Bury ◽

Francesca Baldin ◽

Julie Graff ◽

Emile Van Schaftingen ◽

...

Keyword(s):

Dna Damage ◽

Cell Lines ◽

Oxidative Dna Damage ◽

Fold Increase ◽

Metabolic Effects ◽

Phosphoglycerate Mutase ◽

Wild Type ◽

Metabolic Disturbances ◽

Phosphoglycolate Phosphatase ◽

Damage Repair

Abstract Repair of a certain type of oxidative DNA damage leads to the release of phosphoglycolate, which is an inhibitor of triose phosphate isomerase and is predicted to indirectly inhibit phosphoglycerate mutase activity. Thus, we hypothesized that phosphoglycolate might play a role in a metabolic DNA damage response. Here, we determined how phosphoglycolate is formed in cells, elucidated its effects on cellular metabolism and tested whether DNA damage repair might release sufficient phosphoglycolate to provoke metabolic effects. Phosphoglycolate concentrations were below 5 µM in wild-type U2OS and HCT116 cells and remained unchanged when we inactivated phosphoglycolate phosphatase (PGP), the enzyme that is believed to dephosphorylate phosphoglycolate. Treatment of PGP knockout cell lines with glycolate caused an up to 500-fold increase in phosphoglycolate concentrations, which resulted largely from a side activity of pyruvate kinase. This increase was much higher than in glycolate-treated wild-type cells and was accompanied by metabolite changes consistent with an inhibition of phosphoglycerate mutase, most likely due to the removal of the priming phosphorylation of this enzyme. Surprisingly, we found that phosphoglycolate also inhibits succinate dehydrogenase with a Ki value of <10 µM. Thus, phosphoglycolate can lead to profound metabolic disturbances. In contrast, phosphoglycolate concentrations were not significantly changed when we treated PGP knockout cells with Bleomycin or ionizing radiation, which are known to lead to the release of phosphoglycolate by causing DNA damage. Thus, phosphoglycolate concentrations due to DNA damage are too low to cause major metabolic changes in HCT116 and U2OS cells.

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Autophagic degradation of the BCR-ABL oncoprotein and generation of antileukemic responses by arsenic trioxide

Blood ◽

10.1182/blood-2012-01-402578 ◽

2012 ◽

Vol 120 (17) ◽

pp. 3555-3562 ◽

Cited By ~ 82

Author(s):

Dennis J. Goussetis ◽

Elias Gounaris ◽

Edward J. Wu ◽

Eliza Vakana ◽

Bhumika Sharma ◽

...

Keyword(s):

Arsenic Trioxide ◽

Chronic Myelogenous Leukemia ◽

Cathepsin B ◽

Myelogenous Leukemia ◽

Molecular Targeting ◽

Therapeutic Approaches ◽

Subsequent Degradation ◽

Autophagic Degradation ◽

Partial Reversal

Abstract We provide evidence that arsenic trioxide (As2O3) targets the BCR-ABL oncoprotein via a novel mechanism involving p62/SQSTM1-mediated localization of the oncoprotein to the autolysosomes and subsequent degradation mediated by the protease cathepsin B. Our studies demonstrate that inhibitors of autophagy or cathepsin B activity and/or molecular targeting of p62/SQSTM1, Atg7, or cathepsin B result in partial reversal of the suppressive effects of AS2O3 on BCR-ABL expressing leukemic progenitors, including primitive leukemic precursors from chronic myelogenous leukemia (CML) patients. Altogether, these findings indicate that autophagic degradation of BCR-ABL is critical for the induction of the antileukemic effects of As2O3 and raise the potential for future therapeutic approaches to target BCR-ABL expressing cells by modulating elements of the autophagic machinery to promote BCR-ABL degradation.

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