For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
71
views
15
references
 Top references
cited by
241
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      11
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Loss of iron triggers PINK1/Parkin-independent mitophagy

      report

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          In this study, we develop a simple assay to identify mitophagy inducers on the basis of the use of fluorescently tagged mitochondria that undergo a colour change on lysosomal delivery. Using this assay, we identify iron chelators as a family of compounds that generate a strong mitophagy response. Iron chelation-induced mitophagy requires that cells undergo glycolysis, but does not require PINK1 stabilization or Parkin activation, and occurs in primary human fibroblasts as well as those isolated from a Parkinson's patient with Parkin mutations. Thus, we have identified and characterized a mitophagy pathway, the induction of which could prove beneficial as a potential therapy for several neurodegenerative diseases in which mitochondrial clearance is advantageous.

          Related collections

          Most cited references15

          • Record: found
          • Abstract: found
          • Article: not found

          Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia.

          Huafeng Zhang, Marta Bosch-Marce, Larissa A Shimoda … (2008)
          Autophagy is a process by which cytoplasmic organelles can be catabolized either to remove defective structures or as a means of providing macromolecules for energy generation under conditions of nutrient starvation. In this study we demonstrate that mitochondrial autophagy is induced by hypoxia, that this process requires the hypoxia-dependent factor-1-dependent expression of BNIP3 and the constitutive expression of Beclin-1 and Atg5, and that in cells subjected to prolonged hypoxia, mitochondrial autophagy is an adaptive metabolic response which is necessary to prevent increased levels of reactive oxygen species and cell death.
          Article 0 comments Cited 556 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Mitochondria supply membranes for autophagosome biogenesis during starvation.

            Dale Hailey, Angelika Rambold, Prasanna Satpute-Krishnan … (2010)
            Starvation-induced autophagosomes engulf cytosol and/or organelles and deliver them to lysosomes for degradation, thereby resupplying depleted nutrients. Despite advances in understanding the molecular basis of this process, the membrane origin of autophagosomes remains unclear. Here, we demonstrate that, in starved cells, the outer membrane of mitochondria participates in autophagosome biogenesis. The early autophagosomal marker, Atg5, transiently localizes to punctae on mitochondria, followed by the late autophagosomal marker, LC3. The tail-anchor of an outer mitochondrial membrane protein also labels autophagosomes and is sufficient to deliver another outer mitochondrial membrane protein, Fis1, to autophagosomes. The fluorescent lipid NBD-PS (converted to NBD-phosphotidylethanolamine in mitochondria) transfers from mitochondria to autophagosomes. Photobleaching reveals membranes of mitochondria and autophagosomes are transiently shared. Disruption of mitochondria/ER connections by mitofusin2 depletion dramatically impairs starvation-induced autophagy. Mitochondria thus play a central role in starvation-induced autophagy, contributing membrane to autophagosomes. Copyright (c) 2010 Elsevier Inc. All rights reserved.
            Article 0 comments Cited 454 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              PINK1 is activated by mitochondrial membrane potential depolarization and stimulates Parkin E3 ligase activity by phosphorylating Serine 65

              Chandana Kondapalli, Agne Kazlauskaite, Ning Zhang … (2012)
              Summary Missense mutations in PTEN-induced kinase 1 (PINK1) cause autosomal-recessive inherited Parkinson's disease (PD). We have exploited our recent discovery that recombinant insect PINK1 is catalytically active to test whether PINK1 directly phosphorylates 15 proteins encoded by PD-associated genes as well as proteins reported to bind PINK1. We have discovered that insect PINK1 efficiently phosphorylates only one of these proteins, namely the E3 ligase Parkin. We have mapped the phosphorylation site to a highly conserved residue within the Ubl domain of Parkin at Ser65. We show that human PINK1 is specifically activated by mitochondrial membrane potential (Δψm) depolarization, enabling it to phosphorylate Parkin at Ser65. We further show that phosphorylation of Parkin at Ser65 leads to marked activation of its E3 ligase activity that is prevented by mutation of Ser65 or inactivation of PINK1. We provide evidence that once activated, PINK1 autophosphorylates at several residues, including Thr257, which is accompanied by an electrophoretic mobility band-shift. These results provide the first evidence that PINK1 is activated following Δψm depolarization and suggest that PINK1 directly phosphorylates and activates Parkin. Our findings indicate that monitoring phosphorylation of Parkin at Ser65 and/or PINK1 at Thr257 represent the first biomarkers for examining activity of the PINK1-Parkin signalling pathway in vivo. Our findings also suggest that small molecule activators of Parkin that mimic the effect of PINK1 phosphorylation may confer therapeutic benefit for PD.
              Article 0 comments Cited 390 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): EMBO Rep
                Journal ID (iso-abbrev): EMBO Rep
                Title: EMBO Reports
                Publisher: Nature Publishing Group
                ISSN (Print): 1469-221X
                ISSN (Electronic): 1469-3178
                Publication date (Print): December 2013
                Publication date (Electronic): 01 November 2013
                Publication date PMC-release: 01 November 2013
                Volume: 14
                Issue: 12
                Pages: 1127-1135
                Affiliations
                [1 ]MRC-Protein Phosphorylation and Ubiquitylation Unit , and
                [2 ]Cell Signalling and Immunology, College of Life Sciences, University of Dundee , Dundee DD1 5EH, UK
                Author notes
                [a ]Tel:+01382 388905; Fax:+01382 223778;E-mail: i.ganley@ 123456dundee.ac.uk
                Article
                Publisher Item ID: embor2013168
                DOI: 10.1038/embor.2013.168
                PMC ID: 3981094
                PubMed ID: 24176932
                SO-VID: a032b682-31d8-4a71-bab1-0049ea607203
                Copyright © Copyright © 2013, European Molecular Biology Organization
                License:

                This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. To view a copy of this licence visit http://creativecommons.org/licenses/by/3.0/.

                History
                Date received : 04 June 2013
                Date revision received : 30 September 2013
                Date accepted : 01 October 2013
                Categories
                Subject: Scientific Reports

                ScienceOpen disciplines: Molecular biology
                Keywords: autophagy,iron/mitophagy,pink1,parkin
                Data availability:
                ScienceOpen disciplines: Molecular biology
                Keywords: autophagy, iron/mitophagy, pink1, parkin

                Comments

                Comment on this article

                scite_

                Similar content11

                See all similar

                Cited by235

                See all cited by

                Most referenced authors458

                See all reference authors