For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
15
views
139
references
 Top references
cited by
84
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      1,069
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Role and Mechanisms of Mitophagy in Liver Diseases

      review-article
      Author(s): 1 , 1 , 2 , 1 , *
      Publication date (Electronic):
      Journal: Cells
      Publisher: MDPI
      Keywords: alcohol, autophagy, mitochondria, NAFLD, Parkin, Pink1

      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

          The mitochondrion is an organelle that plays a vital role in the regulation of hepatic cellular redox, lipid metabolism, and cell death. Mitochondrial dysfunction is associated with both acute and chronic liver diseases with emerging evidence indicating that mitophagy, a selective form of autophagy for damaged/excessive mitochondria, plays a key role in the liver’s physiology and pathophysiology. This review will focus on mitochondrial dynamics, mitophagy regulation, and their roles in various liver diseases (alcoholic liver disease, non-alcoholic fatty liver disease, drug-induced liver injury, hepatic ischemia-reperfusion injury, viral hepatitis, and cancer) with the hope that a better understanding of the molecular events and signaling pathways in mitophagy regulation will help identify promising targets for the future treatment of liver diseases.

          Related collections

          Most cited references139

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

          Nix is a selective autophagy receptor for mitochondrial clearance.

          Ivana Novak, Vladimir Kirkin, David G McEwan … (2010)
          Autophagy is the cellular homeostatic pathway that delivers large cytosolic materials for degradation in the lysosome. Recent evidence indicates that autophagy mediates selective removal of protein aggregates, organelles and microbes in cells. Yet, the specificity in targeting a particular substrate to the autophagy pathway remains poorly understood. Here, we show that the mitochondrial protein Nix is a selective autophagy receptor by binding to LC3/GABARAP proteins, ubiquitin-like modifiers that are required for the growth of autophagosomal membranes. In cultured cells, Nix recruits GABARAP-L1 to damaged mitochondria through its amino-terminal LC3-interacting region. Furthermore, ablation of the Nix:LC3/GABARAP interaction retards mitochondrial clearance in maturing murine reticulocytes. Thus, Nix functions as an autophagy receptor, which mediates mitochondrial clearance after mitochondrial damage and during erythrocyte differentiation.
          Article 0 comments Cited 435 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 383 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: not found
              • Article: not found

              Essential role for Nix in autophagic maturation of erythroid cells.

              Swapan K. Dasgupta, Josef T Prchal, Jin-Wang Wei … (2008)
              Erythroid cells undergo enucleation and the removal of organelles during terminal differentiation. Although autophagy has been suggested to mediate the elimination of organelles for erythroid maturation, the molecular mechanisms underlying this process remain undefined. Here we report a role for a Bcl-2 family member, Nix (also called Bnip3L), in the regulation of erythroid maturation through mitochondrial autophagy. Nix(-/-) mice developed anaemia with reduced mature erythrocytes and compensatory expansion of erythroid precursors. Erythrocytes in the peripheral blood of Nix(-/-) mice exhibited mitochondrial retention and reduced lifespan in vivo. Although the clearance of ribosomes proceeded normally in the absence of Nix, the entry of mitochondria into autophagosomes for clearance was defective. Deficiency in Nix inhibited the loss of mitochondrial membrane potential (DeltaPsi(m)), and treatment with uncoupling chemicals or a BH3 mimetic induced the loss of DeltaPsi(m) and restored the sequestration of mitochondria into autophagosomes in Nix(-/-) erythroid cells. These results suggest that Nix-dependent loss of DeltaPsi(m) is important for targeting the mitochondria into autophagosomes for clearance during erythroid maturation, and interference with this function impairs erythroid maturation and results in anaemia. Our study may also provide insights into molecular mechanisms underlying mitochondrial quality control involving mitochondrial autophagy.
              Article 0 comments Cited 380 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): Cells
                Journal ID (iso-abbrev): Cells
                Journal ID (publisher-id): cells
                Title: Cells
                Publisher: MDPI
                ISSN (Electronic): 2073-4409
                Publication date (Electronic): 31 March 2020
                Publication date Collection: April 2020
                Volume: 9
                Issue: 4
                Electronic Location Identifier: 837
                Affiliations
                [1 ]Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS 66160, USA; xma3@ 123456kumc.edu (X.M.); tmckeen@ 123456kumc.edu (T.M.)
                [2 ]Department of Pathology, Division of Molecular Cellular Pathology, University of Alabama at Birmingham, 901 19th street South, Birmingham, AL 35294, USA; jianhuazhang@ 123456uabmc.edu
                Author notes
                [* ]Correspondence: wxding@ 123456kumc.edu ; Tel.: +1-913-588-9813
                Article
                Publisher ID: cells-09-00837
                DOI: 10.3390/cells9040837
                PMC ID: 7226762
                PubMed ID: 32244304
                SO-VID: 22e67557-3e39-4b15-9cdd-ccabd09e6d4e
                Copyright © © 2020 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 13 February 2020
                Date accepted : 28 March 2020
                Categories
                Subject: Review

                Keywords: alcohol,autophagy,mitochondria,nafld,parkin,pink1
                Data availability:
                Keywords: alcohol, autophagy, mitochondria, nafld, parkin, pink1

                Comments

                Comment on this article

                scite_

                Similar content1,069

                See all similar

                Cited by82

                See all cited by

                Most referenced authors3,593

                See all reference authors