AMPK, a Regulator of Metabolism and Autophagy, Is Activated by Lysosomal Damage via a Novel Galectin-Directed Ubiquitin Signal Transduction System.
AMP-Activated Protein Kinases
/ genetics
Adolescent
Adult
Animals
Autophagy
/ drug effects
Energy Metabolism
/ drug effects
Enzyme Activation
Female
Galectins
/ genetics
HEK293 Cells
HeLa Cells
Humans
Hypoglycemic Agents
/ pharmacology
Lysosomes
/ drug effects
MAP Kinase Kinase Kinases
/ genetics
Male
Metformin
/ pharmacology
Mice, Inbred C57BL
Mice, Knockout
Mycobacterium tuberculosis
/ pathogenicity
Signal Transduction
THP-1 Cells
TNF-Related Apoptosis-Inducing Ligand
/ pharmacology
Ubiquitin
/ metabolism
Ubiquitin Thiolesterase
/ genetics
Ubiquitination
Young Adult
ESCRT
LKB1
TAK1
TOR
TRAIL
autophagosome
diabetes
metabolism
metformin
tuberculosis
Journal
Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571
Informations de publication
Date de publication:
05 03 2020
05 03 2020
Historique:
received:
30
07
2019
revised:
27
10
2019
accepted:
24
12
2019
pubmed:
30
1
2020
medline:
7
7
2020
entrez:
30
1
2020
Statut:
ppublish
Résumé
AMPK is a central regulator of metabolism and autophagy. Here we show how lysosomal damage activates AMPK. This occurs via a hitherto unrecognized signal transduction system whereby cytoplasmic sentinel lectins detect membrane damage leading to ubiquitination responses. Absence of Galectin 9 (Gal9) or loss of its capacity to recognize lumenal glycans exposed during lysosomal membrane damage abrogate such ubiquitination responses. Proteomic analyses with APEX2-Gal9 have revealed global changes within the Gal9 interactome during lysosomal damage. Gal9 association with lysosomal glycoproteins increases whereas interactions with a newly identified Gal9 partner, deubiquitinase USP9X, diminishes upon lysosomal injury. In response to damage, Gal9 displaces USP9X from complexes with TAK1 and promotes K63 ubiquitination of TAK1 thus activating AMPK on damaged lysosomes. This triggers autophagy and contributes to autophagic control of membrane-damaging microbe Mycobacterium tuberculosis. Thus, galectin and ubiquitin systems converge to activate AMPK and autophagy during endomembrane homeostasis.
Identifiants
pubmed: 31995728
pii: S1097-2765(19)30958-X
doi: 10.1016/j.molcel.2019.12.028
pmc: PMC7785494
mid: NIHMS1569424
pii:
doi:
Substances chimiques
Galectins
0
Hypoglycemic Agents
0
LGALS9 protein, human
0
TNF-Related Apoptosis-Inducing Ligand
0
USP9X protein, human
0
Ubiquitin
0
galectin 9, mouse
0
Metformin
9100L32L2N
AMPK alpha1 subunit, mouse
EC 2.7.11.1
AMPK alpha2 subunit, mouse
EC 2.7.11.1
PRKAA2 protein, human
EC 2.7.11.1
MAP Kinase Kinase Kinases
EC 2.7.11.25
MAP kinase kinase kinase 7
EC 2.7.11.25
AMP-Activated Protein Kinases
EC 2.7.11.31
PRKAA1 protein, human
EC 2.7.11.31
Ubiquitin Thiolesterase
EC 3.4.19.12
Usp9x protein, mouse
EC 3.4.19.12
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
951-969.e9Subventions
Organisme : NIAID NIH HHS
ID : R01 AI042999
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM121176
Pays : United States
Organisme : NIAID NIH HHS
ID : R37 AI042999
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI111935
Pays : United States
Organisme : NIH HHS
ID : S10 OD021801
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001449
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests M.Z. was an employee of Human Metabolome Technologies America, Boston, MA, USA.
Références
Nature. 2015 Aug 20;524(7565):309-314
pubmed: 26266977
Int J Mol Sci. 2018 Aug 15;19(8):
pubmed: 30111748
Nat Cell Biol. 2018 Feb;20(2):135-143
pubmed: 29230017
Front Immunol. 2017 Dec 15;8:1827
pubmed: 29326710
Mol Cell. 2014 Jan 23;53(2):167-78
pubmed: 24462201
Nat Immunol. 2010 Oct;11(10):897-904
pubmed: 20835230
Cell. 2019 Jan 10;176(1-2):11-42
pubmed: 30633901
Curr Biol. 2014 Mar 17;24(6):609-20
pubmed: 24613307
Nat Cell Biol. 2013 Apr;15(4):406-16
pubmed: 23524951
Nature. 2007 Apr 19;446(7138):916-920
pubmed: 17392790
Science. 2009 Jul 24;325(5939):473-7
pubmed: 19556463
Nat Rev Mol Cell Biol. 2018 Sep;19(9):579-593
pubmed: 30006559
Science. 2010 Dec 3;330(6009):1344-8
pubmed: 21127245
Cell Metab. 2014 Dec 2;20(6):939-52
pubmed: 25448702
J Biol Chem. 2009 May 1;284(18):12297-305
pubmed: 19258318
J Clin Invest. 2001 Oct;108(8):1167-74
pubmed: 11602624
Cell. 2010 Mar 19;140(6):821-32
pubmed: 20303873
Nat Med. 2018 Feb;24(2):213-223
pubmed: 29291351
J Biol Chem. 2005 Feb 25;280(8):7359-68
pubmed: 15590691
Nat Rev Endocrinol. 2018 Jun;14(6):356-376
pubmed: 29686432
J Exp Med. 2015 Jun 29;212(7):979-90
pubmed: 26101267
Curr Opin Nephrol Hypertens. 2017 Sep;26(5):375-383
pubmed: 28614117
Nat Cell Biol. 2011 Feb;13(2):132-41
pubmed: 21258367
Cell. 2015 Feb 12;160(4):715-728
pubmed: 25679763
Cell Host Microbe. 2009 Aug 20;6(2):137-49
pubmed: 19683680
Nature. 2013 Jan 31;493(7434):674-8
pubmed: 23254930
Nat Cell Biol. 2013 Jun;15(6):647-58
pubmed: 23604321
Cell Host Microbe. 2014 Apr 9;15(4):403-11
pubmed: 24721569
Nat Rev Mol Cell Biol. 2018 Jun;19(6):349-364
pubmed: 29618831
Nature. 2010 Jan 7;463(7277):103-7
pubmed: 20023629
Cell Metab. 2012 Apr 4;15(4):534-44
pubmed: 22440612
mBio. 2017 Jul 25;8(4):
pubmed: 28743815
EMBO Rep. 2018 Jul;19(7):
pubmed: 29895712
Mol Cell. 2015 May 7;58(3):507-21
pubmed: 25891078
Proc Natl Acad Sci U S A. 2019 Apr 9;116(15):7288-7297
pubmed: 30914461
Cell Metab. 2017 May 2;25(5):1037-1043
pubmed: 28467923
EMBO J. 2013 Aug 28;32(17):2336-47
pubmed: 23921551
Cell Metab. 2018 Feb 6;27(2):299-313
pubmed: 29153408
Proc Natl Acad Sci U S A. 2011 Nov 29;108(48):19341-6
pubmed: 22084099
Science. 2018 Apr 6;360(6384):
pubmed: 29622626
Cell Host Microbe. 2012 May 17;11(5):469-80
pubmed: 22607800
Cell Metab. 2013 Oct 1;18(4):546-55
pubmed: 24093678
Science. 2011 Jan 28;331(6016):456-61
pubmed: 21205641
EMBO J. 2017 Jan 17;36(2):135-150
pubmed: 27753622
Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17378-83
pubmed: 17085580
J Biol Chem. 2006 Sep 1;281(35):25336-43
pubmed: 16835226
Nature. 2008 Feb 28;451(7182):1069-75
pubmed: 18305538
Nat Rev Immunol. 2013 Oct;13(10):722-37
pubmed: 24064518
Cell Death Differ. 2011 Oct;18(10):1547-60
pubmed: 21331078
Cell Metab. 2019 Mar 5;29(3):592-610
pubmed: 30840912
Nature. 2009 Apr 30;458(7242):1131-5
pubmed: 19339967
J Immunol. 2019 Jul 1;203(1):259-268
pubmed: 31127032
Nature. 2012 Jan 15;482(7385):414-8
pubmed: 22246324
J Biol Chem. 2000 Mar 24;275(12):8355-60
pubmed: 10722666
Cell Metab. 2015 Feb 3;21(2):159-162
pubmed: 25651170
J Biol Chem. 2014 Nov 21;289(47):32926-36
pubmed: 25288801
Science. 2017 Nov 10;358(6364):807-813
pubmed: 29074583
Cell. 2017 Mar 9;168(6):960-976
pubmed: 28283069
Nat Immunol. 2005 Dec;6(12):1245-52
pubmed: 16286920
Cell. 2004 Dec 17;119(6):753-66
pubmed: 15607973
Mol Cell. 2017 Jun 15;66(6):789-800
pubmed: 28622524
Nature. 2001 Jul 19;412(6844):346-51
pubmed: 11460167
Sci Rep. 2015 Aug 04;5:12738
pubmed: 26240016
Genes Dev. 2011 Sep 15;25(18):1895-908
pubmed: 21937710
Dev Cell. 2015 Mar 23;32(6):678-92
pubmed: 25752962
Dev Cell. 2016 Oct 10;39(1):13-27
pubmed: 27693506
Cell Metab. 2016 Oct 11;24(4):521-522
pubmed: 27732831
J Clin Invest. 2014 Aug;124(8):3489-500
pubmed: 25036708
Nature. 2010 Jun 17;465(7300):942-6
pubmed: 20526321
Nature. 2017 Aug 3;548(7665):112-116
pubmed: 28723898
Proc Natl Acad Sci U S A. 2017 Aug 8;114(32):8574-8579
pubmed: 28743755
Science. 2018 May 18;360(6390):751-758
pubmed: 29700228
Semin Cell Biol. 1990 Dec;1(6):441-8
pubmed: 2103895
J Cell Biol. 2005 Nov 21;171(4):603-14
pubmed: 16286508
Science. 2017 Mar 24;355(6331):1306-1311
pubmed: 28336668
J Diabetes Investig. 2015 Nov;6(6):600-9
pubmed: 26543531
J Exp Med. 2007 Jun 11;204(6):1475-85
pubmed: 17548520
Nat Rev Immunol. 2016 Sep;16(9):553-65
pubmed: 27396447
EMBO J. 2009 Mar 18;28(6):677-85
pubmed: 19197243
ACS Chem Biol. 2013 Mar 15;8(3):643-50
pubmed: 23272696
EMBO J. 2011 Nov 11;30(24):4908-20
pubmed: 22081109
Mol Cell. 2018 Apr 5;70(1):120-135.e8
pubmed: 29625033
J Cell Biol. 2001 Jan 8;152(1):165-80
pubmed: 11149929
Cell Microbiol. 2010 Apr 1;12(4):530-44
pubmed: 19951367
Cell. 2013 Jan 17;152(1-2):290-303
pubmed: 23332761
Proc Natl Acad Sci U S A. 1990 Jan;87(1):83-7
pubmed: 2296607
Curr Biol. 2003 Nov 11;13(22):2004-8
pubmed: 14614828
EMBO J. 2018 Nov 2;37(21):
pubmed: 30314966
Cancer Genet Cytogenet. 2010 Mar;197(2):130-41
pubmed: 20193846
J Exp Med. 2010 Oct 25;207(11):2343-54
pubmed: 20937702
J Biol Chem. 2016 Aug 26;291(35):18591-9
pubmed: 27435670
Mol Cell. 2009 May 15;34(3):259-69
pubmed: 19450525
Science. 2011 Jun 17;332(6036):1429-33
pubmed: 21617040
Biochem J. 1994 May 15;300 ( Pt 1):229-36
pubmed: 8198538
Front Cardiovasc Med. 2015 May 19;2:25
pubmed: 26664897
Cell Metab. 2005 Jul;2(1):9-19
pubmed: 16054095
Nat Rev Mol Cell Biol. 2018 Feb;19(2):121-135
pubmed: 28974774
Cell Metab. 2014 Sep 2;20(3):526-40
pubmed: 25002183
J Biol Chem. 2010 Feb 19;285(8):5347-60
pubmed: 20038579
Mol Biol Cell. 2009 Apr;20(7):1992-2003
pubmed: 19225151
PLoS Biol. 2013 Nov;11(11):e1001708
pubmed: 24265594
Nat Commun. 2014 Dec 04;5:5637
pubmed: 25472497
J Biochem. 2012 Feb;151(2):157-66
pubmed: 21976705
Cell Metab. 2014 Dec 2;20(6):953-66
pubmed: 25456737
Cell Death Dis. 2018 May 11;9(5):570
pubmed: 29752434
Elife. 2017 Apr 10;6:
pubmed: 28394250
DNA Repair (Amst). 2019 Apr;76:30-39
pubmed: 30807924
Autophagy. 2015;11(8):1408-24
pubmed: 26114578
J Cell Biol. 2013 Oct 14;203(1):115-28
pubmed: 24100292
Nature. 2015 Jun 18;522(7556):354-8
pubmed: 26040720
J Cell Sci. 2018 May 1;131(9):
pubmed: 29717004
J Cell Biol. 1990 Sep;111(3):941-53
pubmed: 2391370
Autophagy. 2019 Jun;15(6):1082-1099
pubmed: 30654731
Oncogene. 2018 May;37(18):2422-2431
pubmed: 29449692
J Biol Chem. 2008 Sep 5;283(36):24497-505
pubmed: 18617512
Nat Rev Rheumatol. 2017 May;13(5):267-279
pubmed: 28331208
Mol Cell. 2016 Jan 7;61(1):84-97
pubmed: 26687681
Mol Biol Cell. 2009 Apr;20(7):1981-91
pubmed: 19211835
J Biol Chem. 2007 Sep 28;282(39):28960-70
pubmed: 17686764
Biochem J. 2008 Apr 15;411(2):249-60
pubmed: 18254724
Cell Metab. 2019 Sep 3;30(3):508-524.e12
pubmed: 31204282