دورية أكاديمية
FBXL4 suppresses mitophagy by restricting the accumulation of NIX and BNIP3 mitophagy receptors.
| العنوان: | FBXL4 suppresses mitophagy by restricting the accumulation of NIX and BNIP3 mitophagy receptors. |
|---|---|
| المؤلفون: | Nguyen-Dien GT; Faculty of Medicine, School of Biomedical Sciences, University of Queensland, Brisbane, QLD, Australia.; Department of Biotechnology, School of Biotechnology, Viet Nam National University-International University, Ho Chi Minh City, Vietnam., Kozul KL; Faculty of Medicine, School of Biomedical Sciences, University of Queensland, Brisbane, QLD, Australia., Cui Y; Faculty of Medicine, School of Biomedical Sciences, University of Queensland, Brisbane, QLD, Australia., Townsend B; Faculty of Medicine, School of Biomedical Sciences, University of Queensland, Brisbane, QLD, Australia., Kulkarni PG; Faculty of Medicine, School of Biomedical Sciences, University of Queensland, Brisbane, QLD, Australia., Ooi SS; Faculty of Medicine, School of Biomedical Sciences, University of Queensland, Brisbane, QLD, Australia., Marzio A; Department of Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine, New York, NY, USA.; Perlmutter Cancer Center, New York University Grossman School of Medicine, New York, NY, USA.; Department of Pathology and Lab Medicine, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA., Carrodus N; Faculty of Medicine, School of Biomedical Sciences, University of Queensland, Brisbane, QLD, Australia., Zuryn S; Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia., Pagano M; Department of Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine, New York, NY, USA.; Perlmutter Cancer Center, New York University Grossman School of Medicine, New York, NY, USA., Parton RG; Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia.; Centre for Microscopy and Microanalysis, University of Queensland, Brisbane, QLD, Australia., Lazarou M; Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.; Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Melbourne, VIC, Australia.; Department of Medical Biology, University of Melbourne, Melbourne, VIC, Australia., Millard SS; Faculty of Medicine, School of Biomedical Sciences, University of Queensland, Brisbane, QLD, Australia., Taylor RW; Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.; NHS Highly Specialised Service for Rare Mitochondrial Disorders, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK., Collins BM; Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia., Jones MJ; The University of Queensland Diamantina Institute, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.; School of Chemistry & Molecular Biosciences, University of Queensland, Brisbane, QLD, Australia., Pagan JK; Faculty of Medicine, School of Biomedical Sciences, University of Queensland, Brisbane, QLD, Australia.; Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia.; The University of Queensland Diamantina Institute, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia. |
| المصدر: | The EMBO journal [EMBO J] 2023 Jul 03; Vol. 42 (13), pp. e112767. Date of Electronic Publication: 2023 May 10. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 8208664 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1460-2075 (Electronic) Linking ISSN: 02614189 NLM ISO Abbreviation: EMBO J Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2024- : [London] : Nature Publishing Group Original Publication: Eynsham, Oxford, England : Published for the European Molecular Biology Organization by IRL Press, [c1982- |
| مواضيع طبية MeSH: | Mitophagy*/physiology , Phagocytosis*, Autophagy/physiology ; DNA, Mitochondrial/metabolism ; Mitochondria/metabolism ; Mitochondrial Proteins/genetics ; Mitochondrial Proteins/metabolism ; Humans ; Animals ; Mice |
| مستخلص: | To maintain both mitochondrial quality and quantity, cells selectively remove damaged or excessive mitochondria through mitophagy, which is a specialised form of autophagy. Mitophagy is induced in response to diverse conditions, including hypoxia, cellular differentiation and mitochondrial damage. However, the mechanisms that govern the removal of specific dysfunctional mitochondria under steady-state conditions to fine-tune mitochondrial content are not well understood. Here, we report that SCF FBXL4 , an SKP1/CUL1/F-box protein ubiquitin ligase complex, localises to the mitochondrial outer membrane in unstressed cells and mediates the constitutive ubiquitylation and degradation of the mitophagy receptors NIX and BNIP3 to suppress basal levels of mitophagy. We demonstrate that the pathogenic variants of FBXL4 that cause encephalopathic mtDNA depletion syndrome (MTDPS13) do not efficiently interact with the core SCF ubiquitin ligase machinery or mediate the degradation of NIX and BNIP3. Thus, we reveal a molecular mechanism whereby FBXL4 actively suppresses mitophagy by preventing NIX and BNIP3 accumulation. We propose that the dysregulation of NIX and BNIP3 turnover causes excessive basal mitophagy in FBXL4-associated mtDNA depletion syndrome. (© 2023 The Authors. Published under the terms of the CC BY 4.0 license.) |
| التعليقات: | Comment in: EMBO J. 2023 Jul 3;42(13):e114542. (PMID: 37272260) |
| References: | EMBO Rep. 2014 May;15(5):566-75. (PMID: 24671035) Bioinformatics. 2019 Aug 15;35(16):2856-2858. (PMID: 30615063) Nat Cell Biol. 2012 Jan 22;14(2):177-85. (PMID: 22267086) Nature. 2021 Aug;596(7873):583-589. (PMID: 34265844) J Cell Biol. 2008 Dec 1;183(5):795-803. (PMID: 19029340) Proc Natl Acad Sci U S A. 2015 Apr 14;112(15):4630-5. (PMID: 25827227) Biochim Biophys Acta Mol Basis Dis. 2019 Nov 1;1865(11):165536. (PMID: 31442532) Cancer Res. 2005 Oct 1;65(19):9047-55. (PMID: 16204079) Cell Chem Biol. 2021 Jul 15;28(7):918-933. (PMID: 33974914) EMBO J. 2017 Jun 14;36(12):1688-1706. (PMID: 28465321) Nature. 1999 May 20;399(6733):271-5. (PMID: 10353251) EMBO J. 2023 Jul 3;42(13):e112767. (PMID: 37161784) Autophagy. 2022 Feb;18(2):467-469. (PMID: 35001811) Nat Commun. 2017 Mar 09;8:14697. (PMID: 28276439) Mol Cell Biol. 2009 May;29(10):2570-81. (PMID: 19273585) Cancer Res. 2001 Sep 15;61(18):6669-73. (PMID: 11559532) J Cell Biol. 2010 Nov 29;191(5):933-42. (PMID: 21115803) Cell Metab. 2018 Feb 6;27(2):439-449.e5. (PMID: 29337137) Am J Hum Genet. 2013 Sep 5;93(3):471-81. (PMID: 23993193) Nature. 2021 Apr;592(7856):789-793. (PMID: 33854235) Cell Stress. 2020 Mar 04;4(5):99-113. (PMID: 32420530) J Biol Chem. 2008 Apr 18;283(16):10892-903. (PMID: 18281291) Nat Methods. 2022 Jun;19(6):679-682. (PMID: 35637307) J Biol Chem. 2013 Nov 8;288(45):32766-32776. (PMID: 24085301) Sci Rep. 2017 Apr 25;7(1):1131. (PMID: 28442745) Nucleic Acids Res. 1988 Feb 11;16(3):1215. (PMID: 3344216) Am J Hum Genet. 2013 Sep 5;93(3):482-95. (PMID: 23993194) J Biol Chem. 2012 Jun 1;287(23):19094-104. (PMID: 22505714) Mol Cell. 2014 May 8;54(3):362-77. (PMID: 24746696) Nature. 2009 Apr 9;458(7239):732-6. (PMID: 19360080) Science. 2001 Apr 20;292(5516):464-8. (PMID: 11292862) Nature. 2013 Apr 4;496(7443):64-8. (PMID: 23503662) Nat Cell Biol. 2015 Jan;17(1):31-43. (PMID: 25503564) EMBO Rep. 2013 Dec;14(12):1050-61. (PMID: 24232186) PLoS Comput Biol. 2017 Jul 26;13(7):e1005659. (PMID: 28746339) Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19500-5. (PMID: 18048346) Annu Rev Biochem. 2021 Jun 20;90:403-429. (PMID: 33823649) Front Genet. 2019 Feb 05;10:39. (PMID: 30804983) EMBO J. 2021 Feb 1;40(3):e104705. (PMID: 33438778) EMBO Rep. 2010 Jan;11(1):45-51. (PMID: 20010802) Science. 2001 Apr 20;292(5516):468-72. (PMID: 11292861) J Cell Biol. 2018 May 7;217(5):1613-1622. (PMID: 29500189) Nat Protoc. 2017 Aug;12(8):1576-1587. (PMID: 28703790) Curr Biol. 2018 Feb 19;28(4):R170-R185. (PMID: 29462587) Nat Rev Mol Cell Biol. 2013 Jun;14(6):369-81. (PMID: 23657496) Cell Rep. 2021 Feb 2;34(5):108689. (PMID: 33535046) EMBO J. 2022 Dec 15;41(24):e111115. (PMID: 36215693) EMBO Mol Med. 2020 Jul 7;12(7):e11659. (PMID: 32525278) Nature. 2015 Aug 20;524(7565):309-314. (PMID: 26266977) Cell. 2011 Oct 14;147(2):459-74. (PMID: 21963094) Nature. 2008 Jul 10;454(7201):232-5. (PMID: 18454133) EMBO Rep. 2013 Dec;14(12):1127-35. (PMID: 24176932) Autophagy. 2021 May;17(5):1232-1243. (PMID: 32286918) |
| معلومات مُعتمدة: | T32 CA009161 United States CA NCI NIH HHS; United Kingdom DH_ Department of Health; MR/W019027/1 United Kingdom MRC_ Medical Research Council; MR/S005021/1 United Kingdom MRC_ Medical Research Council; 203105/Z/16/Z United Kingdom WT_ Wellcome Trust; R35 GM136250 United States GM NIGMS NIH HHS; T32CA009161 United States CA NCI NIH HHS; United Kingdom WT_ Wellcome Trust |
| فهرسة مساهمة: | Keywords: BNIP3; FBXL4; NIX/BNIP3L; mitochondria; mitophagy |
| المشرفين على المادة: | 0 (DNA, Mitochondrial) 0 (Mitochondrial Proteins) |
| تواريخ الأحداث: | Date Created: 20230510 Date Completed: 20230630 Latest Revision: 20240210 |
| رمز التحديث: | 20240210 |
| مُعرف محوري في PubMed: | PMC10308361 |
| DOI: | 10.15252/embj.2022112767 |
| PMID: | 37161784 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder كن أول من يترك تعليقا!