ESCRT-mediated phagophore sealing during mitophagy.
ESCRT
macroautophagy
membrane sealing
mitophagy
phagophore
Journal
Autophagy
ISSN: 1554-8635
Titre abrégé: Autophagy
Pays: United States
ID NLM: 101265188
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
pubmed:
2
8
2019
medline:
8
6
2021
entrez:
2
8
2019
Statut:
ppublish
Résumé
Inactivation of the endosomal sorting complex required for transport (ESCRT) machinery has been reported to cause autophagic defects, but the exact functions of ESCRT proteins in macroautophagy/autophagy remain incompletely understood. Using live-cell fluorescence microscopy we found that the filament-forming ESCRT-III subunit CHMP4B was recruited transiently to nascent autophagosomes during starvation-induced autophagy and mitophagy, with residence times of about 1 and 2 min, respectively. Correlative light microscopy and electron tomography revealed CHMP4B recruitment at a late step in mitophagosome formation. The autophagosomal dwell time of CHMP4B was strongly increased by depletion of the regulatory ESCRT-III subunit CHMP2A. Using a novel optogenetic closure assay we observed that depletion of CHMP2A inhibited phagophore sealing during mitophagy. Consistent with this, depletion of CHMP2A and other ESCRT-III subunits inhibited both PRKN/PARKIN-dependent and -independent mitophagy. We conclude that the ESCRT machinery mediates phagophore closure, and that this is essential for mitophagic flux.
Identifiants
pubmed: 31366282
doi: 10.1080/15548627.2019.1639301
pmc: PMC7158923
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
826-841Références
Nat Cell Biol. 2010 Apr;12(4):362-71
pubmed: 20208530
Curr Pharm Des. 2013;19(30):5437-42
pubmed: 23431986
Nat Rev Mol Cell Biol. 2004 Apr;5(4):317-23
pubmed: 15071556
Science. 2014 Feb 28;343(6174):1247136
pubmed: 24482116
Autophagy. 2016;12(1):1-222
pubmed: 26799652
PLoS One. 2009 Aug 06;4(8):e6529
pubmed: 19657394
Cell Struct Funct. 2002 Feb;27(1):29-37
pubmed: 11937716
Science. 2007 Jun 29;316(5833):1908-12
pubmed: 17556548
Cell. 2012 Dec 7;151(6):1256-69
pubmed: 23217709
J Cell Biol. 2019 Jun 3;218(6):1908-1927
pubmed: 31010855
Cell Struct Funct. 1997 Oct;22(5):501-9
pubmed: 9431454
J Biol Chem. 1998 Aug 21;273(34):21883-92
pubmed: 9705327
Cell. 1990 Jul 27;62(2):317-29
pubmed: 2115402
EMBO Rep. 2018 Apr;19(4):
pubmed: 29437695
Science. 2016 Apr 15;352(6283):353-8
pubmed: 27013428
J Cell Sci. 2012 Feb 1;125(Pt 3):685-94
pubmed: 22389403
Nat Commun. 2018 Jul 20;9(1):2855
pubmed: 30030437
Cold Spring Harb Perspect Biol. 2013 Sep 01;5(9):
pubmed: 24003212
Cell. 2001 Jul 27;106(2):145-55
pubmed: 11511343
Curr Opin Cell Biol. 2010 Apr;22(2):124-31
pubmed: 20034776
J Cell Biol. 2016 Feb 29;212(5):499-513
pubmed: 26929449
Dev Cell. 2002 Aug;3(2):271-82
pubmed: 12194857
Curr Biol. 2007 Sep 18;17(18):1561-7
pubmed: 17683935
J Cell Biol. 2007 Nov 5;179(3):485-500
pubmed: 17984323
Nature. 2015 Jun 11;522(7555):236-9
pubmed: 26040713
Science. 2018 Apr 6;360(6384):
pubmed: 29622626
Curr Biol. 2007 Oct 23;17(20):1817-25
pubmed: 17935992
Dev Cell. 2008 Oct;15(4):578-89
pubmed: 18854142
Nat Rev Mol Cell Biol. 2002 Dec;3(12):893-905
pubmed: 12461556
Science. 2016 Apr 15;352(6283):359-62
pubmed: 27013426
Science. 2011 Mar 25;331(6024):1616-20
pubmed: 21310966
J Cell Biol. 2014 Sep 15;206(6):763-77
pubmed: 25202029
EMBO J. 2015 Oct 1;34(19):2398-407
pubmed: 26311197
Nat Commun. 2018 Jul 26;9(1):2932
pubmed: 30050131
Dev Cell. 2019 May 20;49(4):509-525.e12
pubmed: 30982665
EMBO J. 2018 Nov 2;37(21):
pubmed: 30314966
Curr Biol. 2018 Feb 19;28(4):R170-R185
pubmed: 29462587
Nat Rev Mol Cell Biol. 2017 Jan;18(1):5-17
pubmed: 27703243
Trends Biochem Sci. 2017 Jan;42(1):42-56
pubmed: 27669649
Autophagy. 2015 Nov 2;11(11):2134-2137
pubmed: 26466816
J Cell Sci. 2015 Jan 15;128(2):193-205
pubmed: 25568151
EMBO J. 2000 Nov 1;19(21):5720-8
pubmed: 11060023
Nature. 2015 Jun 11;522(7555):231-5
pubmed: 26040712
J Cell Sci. 2009 Jul 1;122(Pt 13):2179-83
pubmed: 19535733
EMBO Rep. 2013 Dec;14(12):1127-35
pubmed: 24176932
Genome Biol. 2006;7(10):R100
pubmed: 17076895
Nat Methods. 2016 Sep;13(9):755-8
pubmed: 27427858
J Cell Biol. 2014 Nov 10;207(3):419-32
pubmed: 25385186