title: Autophagosome dynamics in neurodegeneration at a glance.
abstract: Autophagy is an essential homeostatic process for degrading cellular cargo. Aging organelles and protein aggregates are degraded by the autophagosome-lysosome pathway, which is particularly crucial in neurons. There is increasing evidence implicating defective autophagy in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Alzheimer's disease, Parkinson's disease and Huntington's disease. Recent work using live-cell imaging has identified autophagy as a predominantly polarized process in neuronal axons; autophagosomes preferentially form at the axon tip and undergo retrograde transport back towards the cell body. Autophagosomes engulf cargo including damaged mitochondria (mitophagy) and protein aggregates, and subsequently fuse with lysosomes during axonal transport to effectively degrade their internalized cargo. In this Cell Science at a Glance article and the accompanying poster, we review recent progress on the dynamics of the autophagy pathway in neurons and highlight the defects observed at each step of this pathway during neurodegeneration.
authors.affiliation: Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104 USA.
authors.forename: Yvette C
authors.initials: YC
authors.lastname: Wong
authors.affiliation: Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104 USA holzbaur@mail.med.upenn.edu.
authors.forename: Erika L F
authors.initials: EL
authors.lastname: Holzbaur
mesh_terms: D000818:Animals; D001343:Autophagy; D006801:Humans; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010588:Phagosomes / Q000235:genetics / Q000378:metabolism*
keywords: Alzheimer's disease; Amyotrophic lateral sclerosis; Autophagy; Axonal transport; Huntington’s disease; Parkinson’s disease
references.citation: Hum Mol Genet. 2005 Sep 1;14(17):2571-86
references.pmid: 16049031
references.citation: Nat Neurosci. 2013 Sep;16(9):1257-65
references.pmid: 23933751
references.citation: Nat Neurosci. 2010 Jul;13(7):805-11
references.pmid: 20581817
references.citation: Nat Chem Biol. 2014 Aug;10(8):677-85
references.pmid: 24974230
references.citation: Cell. 2011 Sep 2;146(5):682-95
references.pmid: 21884931
references.citation: J Neuropathol Exp Neurol. 2011 May;70(5):349-59
references.pmid: 21487309
references.citation: Nature. 2014 Jun 5;510(7503):162-6
references.pmid: 24784582
references.citation: Autophagy. 2014 Oct 1;10(10):1761-75
references.pmid: 25126727
references.citation: Mol Cell. 2014 Jan 23;53(2):167-78
references.pmid: 24462201
references.citation: Hum Mol Genet. 2010 Aug 15;19(16):3219-32
references.pmid: 20529957
references.citation: Hum Mol Genet. 1997 Dec;6(13):2205-12
references.pmid: 9361024
references.citation: Hum Mol Genet. 2012 Feb 1;21(3):511-25
references.pmid: 22012985
references.citation: Nat Genet. 2004 Jun;36(6):585-95
references.pmid: 15146184
references.citation: Mol Cell Biol. 2012 Nov;32(21):4410-8
references.pmid: 22927642
references.citation: EMBO J. 2014 Nov 3;33(21):2473-91
references.pmid: 25216678
references.citation: Nature. 1995 Jun 29;375(6534):754-60
references.pmid: 7596406
references.citation: Proc Natl Acad Sci U S A. 2007 Sep 4;104(36):14489-94
references.pmid: 17726112
references.citation: J Cell Biol. 2010 Nov 29;191(5):933-42
references.pmid: 21115803
references.citation: Autophagy. 2010 Apr;6(3):378-85
references.pmid: 20150763
references.citation: Nat Rev Neurol. 2012 Feb;8(2):108-17
references.pmid: 22187000
references.citation: Nat Neurosci. 2013 Apr;16(4):394-406
references.pmid: 23455607
references.citation: Proc Natl Acad Sci U S A. 2014 Oct 21;111(42):E4439-48
references.pmid: 25294927
references.citation: J Biol Chem. 2013 May 24;288(21):15194-210
references.pmid: 23532841
references.citation: Nat Commun. 2014;5:3496
references.pmid: 24667209
references.citation: Dev Cell. 2014 Jul 14;30(1):71-85
references.pmid: 25026034
references.citation: Autophagy. 2010 Nov;6(8):1090-106
references.pmid: 20890124
references.citation: Proc Natl Acad Sci U S A. 2012 Jun 12;109(24):9611-6
references.pmid: 22647602
references.citation: Nat Cell Biol. 2014 Jun;16(6):495-501
references.pmid: 24875736
references.citation: Nat Genet. 2005 Jul;37(7):771-6
references.pmid: 15980862
references.citation: Trends Cell Biol. 2014 Oct;24(10):564-74
references.pmid: 24953741
references.citation: Genes Cells. 2010 Aug;15(8):887-900
references.pmid: 20604804
references.citation: Nature. 1995 Nov 23;378(6555):398-402
references.pmid: 7477378
references.citation: Biochem J. 2014 May 15;460(1):127-39
references.pmid: 24660806
references.citation: Mol Cell. 2014 Nov 6;56(3):360-75
references.pmid: 25284222
references.citation: Neuron. 2011 Oct 20;72(2):245-56
references.pmid: 21944778
references.citation: Nature. 1998 Apr 9;392(6676):605-8
references.pmid: 9560156
references.citation: Nat Commun. 2014;5:3828
references.pmid: 24819384
references.citation: Mol Cell. 2011 Oct 21;44(2):279-89
references.pmid: 22017874
references.citation: J Biol Chem. 2014 Oct 24;289(43):29519-30
references.pmid: 25217637
references.citation: Nat Commun. 2013;4:2428
references.pmid: 24013556
references.citation: Mol Biol Cell. 2013 Apr;24(8):1153-62
references.pmid: 23427266
references.citation: J Cell Biol. 2010 Sep 20;190(6):1023-37
references.pmid: 20855506
references.citation: Nat Commun. 2014;5:4998
references.pmid: 25241929
references.citation: J Biol Chem. 2006 May 19;281(20):14474-85
references.pmid: 16522639
references.citation: Science. 2011 Jul 8;333(6039):228-33
references.pmid: 21617041
references.citation: J Neurosci. 2011 May 25;31(21):7817-30
references.pmid: 21613495
references.citation: Hum Mol Genet. 2014 Jun 15;23(12):3166-79
references.pmid: 24459296
references.citation: Curr Biol. 2014 Aug 18;24(16):1854-65
references.pmid: 25088558
references.citation: Cell Rep. 2013 Oct 17;5(1):61-9
references.pmid: 24095740
references.citation: EMBO Rep. 2014 Jan;15(1):86-93
references.pmid: 24357652
references.citation: Dis Model Mech. 2008 Sep-Oct;1(2-3):168-74; discussion 173
references.pmid: 19048081
references.citation: PLoS One. 2013;8(2):e54511
references.pmid: 23408943
references.citation: Nat Genet. 2003 Apr;33(4):455-6
references.pmid: 12627231
references.citation: J Cell Sci. 2013 Jan 15;126(Pt 2):580-92
references.pmid: 23178947
references.citation: Cell. 2001 Jun 1;105(5):587-97
references.pmid: 11389829
references.citation: J Biol Chem. 2003 Jul 4;278(27):25009-13
references.pmid: 12719433
references.citation: Neurobiol Aging. 2014 Dec;35(12):2822-31
references.pmid: 25216585
references.citation: J Cell Sci. 2014 Aug 1;127(Pt 15):3280-93
references.pmid: 24906799
references.citation: Nat Neurosci. 2010 May;13(5):567-76
references.pmid: 20383138
references.citation: Curr Biol. 2007 Sep 18;17(18):1561-7
references.pmid: 17683935
references.citation: J Biol Chem. 2013 Feb 22;288(8):5660-72
references.pmid: 23303188
references.citation: J Neurochem. 2011 Jun;117(5):856-67
references.pmid: 21426348
references.citation: Hum Mol Genet. 2010 Oct 1;19(19):3734-46
references.pmid: 20639397
references.citation: J Neurosci. 2014 Jan 22;34(4):1293-305
references.pmid: 24453320
references.citation: Neuron. 2010 Jan 14;65(1):53-65
references.pmid: 20152113
references.citation: Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):378-83
references.pmid: 19966284
references.citation: J Cell Biol. 2010 May 17;189(4):671-9
references.pmid: 20457763
references.citation: EMBO J. 2012 Apr 18;31(8):1853-64
references.pmid: 22446390
references.citation: Science. 2004 May 21;304(5674):1158-60
references.pmid: 15087508
references.citation: J Cell Biol. 2009 Dec 14;187(6):875-88
references.pmid: 20008565
references.citation: Nat Genet. 2009 Feb;41(2):163-5
references.pmid: 19136952
references.citation: EMBO Rep. 2012 Apr;13(4):378-85
references.pmid: 22354088
references.citation: Trends Neurosci. 2010 Jul;33(7):335-44
references.pmid: 20434225
references.citation: Cell. 2009 Apr 3;137(1):60-72
references.pmid: 19345187
references.citation: J Cell Biol. 2005 Nov 21;171(4):603-14
references.pmid: 16286508
references.citation: Hum Mol Genet. 2014 Jul 1;23(13):3579-95
references.pmid: 24549040
references.citation: Hum Mol Genet. 2011 Jan 1;20(1):40-50
references.pmid: 20940149
references.citation: J Cell Sci. 2014 Jan 1;127(Pt 1):3-9
references.pmid: 24345374
references.citation: J Cell Biol. 2014 Apr 28;205(2):143-53
references.pmid: 24751536
references.citation: J Biol Chem. 2009 Oct 2;284(40):27416-24
references.pmid: 19651785
references.citation: J Biol Chem. 2006 Feb 10;281(6):3552-9
references.pmid: 16339760
references.citation: Hum Mol Genet. 2014 Oct 1;23(19):5227-42
references.pmid: 24852371
references.citation: Curr Biol. 2012 Mar 20;22(6):545-52
references.pmid: 22342752
references.citation: Hum Mol Genet. 2009 Nov 1;18(21):4022-34
references.pmid: 19640926
references.citation: Cell. 2013 Jun 20;153(7):1461-74
references.pmid: 23791177
references.citation: Autophagy. 2010 Feb;6(2):217-27
references.pmid: 20104022
references.citation: J Neurosci. 1998 Feb 15;18(4):1261-9
references.pmid: 9454836
references.citation: Nature. 2007 Jun 28;447(7148):1121-5
references.pmid: 17589504
references.citation: Nat Neurosci. 2011 Apr;14(4):459-68
references.pmid: 21358643
references.citation: Neuron. 2013 Apr 10;78(1):65-80
references.pmid: 23498974
references.citation: Neuron. 2014 Oct 22;84(2):292-309
references.pmid: 25374356
references.citation: Nature. 2013 Apr 18;496(7445):372-6
references.pmid: 23503661
references.citation: J Cell Biol. 2014 Sep 1;206(5):655-70
references.pmid: 25154397
references.citation: EMBO Rep. 2013 Dec;14(12):1127-35
references.pmid: 24176932
references.citation: J Neurosci. 2006 Aug 2;26(31):8057-68
references.pmid: 16885219
references.citation: Neuron. 2011 Oct 20;72(2):257-68
references.pmid: 21944779
references.citation: Genes Dev. 2009 Oct 1;23(19):2294-306
references.pmid: 19762508
references.citation: Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10045-50
references.pmid: 17548833
references.citation: Science. 2004 Aug 27;305(5688):1292-5
references.pmid: 15333840
references.citation: PLoS One. 2010;5(3):e9872
references.pmid: 20352044
references.citation: J Neuropathol Exp Neurol. 2005 Feb;64(2):113-22
references.pmid: 15751225
references.citation: PLoS One. 2010;5(3):e9805
references.pmid: 20339559
references.citation: Nat Neurosci. 2012 Nov;15(11):1488-97
references.pmid: 23023293
references.citation: Autophagy. 2013 Nov 1;9(11):1758-69
references.pmid: 24121706
references.citation: J Biol Chem. 2006 Oct 13;281(41):30524-33
references.pmid: 16920710
references.citation: Proc Natl Acad Sci U S A. 2014 Jun 10;111(23):8494-9
references.pmid: 24912190
references.citation: J Cell Sci. 2013 Aug 1;126(Pt 15):3237-47
references.pmid: 23908376
references.citation: Hum Mol Genet. 2007 Nov 1;16(21):2600-15
references.pmid: 17704510
references.citation: Nat Med. 2013 Aug;19(8):983-97
references.pmid: 23921753
references.citation: Cell. 2014 Jul 31;158(3):549-63
references.pmid: 25042851
references.citation: PLoS One. 2013;8(12):e83050
references.pmid: 24376631
references.citation: J Cell Biol. 2006 Feb 27;172(5):719-31
references.pmid: 16505167
references.citation: J Cell Biol. 2012 Feb 20;196(4):407-17
references.pmid: 22331844
references.citation: Neuron. 2010 Dec 9;68(5):857-64
references.pmid: 21145000
references.citation: Open Biol. 2012 May;2(5):120080
references.pmid: 22724072
references.citation: J Cell Biol. 2008 Dec 1;183(5):795-803
references.pmid: 19029340
references.citation: Cell. 2010 Jun 25;141(7):1146-58
references.pmid: 20541250
references.citation: Hum Mol Genet. 2003 Dec 15;12(24):3231-44
references.pmid: 14570716
references.citation: Mol Biol Cell. 2014 Dec 15;25(25):4010-23
references.pmid: 25298402
references.citation: Hum Mol Genet. 2014 Aug 15;23(16):4201-14
references.pmid: 24682598
references.citation: Cell Res. 2014 Jan;24(1):92-104
references.pmid: 24281265
references.citation: Hum Mol Genet. 2002 May 1;11(9):1107-17
references.pmid: 11978769
references.citation: Hum Mol Genet. 2011 Mar 1;20(5):867-79
references.pmid: 21138942
references.citation: Nature. 2006 Jun 15;441(7095):885-9
references.pmid: 16625204
references.citation: Cell Death Differ. 2015 Mar;22(3):419-32
references.pmid: 25215947
references.citation: PLoS Biol. 2010 Jan;8(1):e1000298
references.pmid: 20126261
references.citation: Cell Mol Life Sci. 2012 Apr;69(7):1125-36
references.pmid: 22080117
references.citation: Sci Rep. 2012;2:1002
references.pmid: 23256036
references.citation: Nat Cell Biol. 2010 Sep;12(9):814-22
references.pmid: 20811353
references.citation: J Neurosci. 2012 Mar 21;32(12):4240-6
references.pmid: 22442086
references.citation: Nature. 2010 May 13;465(7295):223-6
references.pmid: 20428114
references.citation: Cell. 2011 Nov 11;147(4):893-906
references.pmid: 22078885
references.citation: Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14164-9
references.pmid: 20660724
references.citation: Proc Natl Acad Sci U S A. 2010 May 25;107(21):9747-52
references.pmid: 20457924
references.citation: J Cell Biol. 2013 Aug 5;202(3):495-508
references.pmid: 23897889
references.citation: Nat Cell Biol. 2013 Oct;15(10):1197-205
references.pmid: 24036476
references.citation: Dev Cell. 2014 Jun 9;29(5):577-90
references.pmid: 24914561
references.citation: Genes Cells. 2013 Dec;18(12):1131-43
references.pmid: 24215292
references.citation: J Cell Sci. 2014 Aug 15;127(Pt 16):3488-504
references.pmid: 24928900
references.citation: J Neurosci. 2008 Jul 2;28(27):6926-37
references.pmid: 18596167
references.citation: J Cell Biol. 2010 Apr 19;189(2):211-21
references.pmid: 20404107
references.citation: J Cell Sci. 2014 Mar 15;127(Pt 6):1263-78
references.pmid: 24424030
references.citation: Neuron. 2013 Feb 6;77(3):425-39
references.pmid: 23395371
references.citation: Front Neurol. 2013 Jul 19;4:100
references.pmid: 23882257
references.citation: J Cell Biol. 2007 Nov 5;179(3):485-500
references.pmid: 17984323
references.citation: J Cell Sci. 2013 Nov 1;126(Pt 21):4843-9
references.pmid: 24006259
references.citation: J Neurosci. 2001 Dec 15;21(24):9549-60
references.pmid: 11739566
references.citation: Arch Neurol. 2011 Nov;68(11):1440-6
references.pmid: 22084127
references.citation: Nature. 2014 Jun 19;510(7505):370-5
references.pmid: 24896179
references.citation: J Cell Biol. 2010 Dec 27;191(7):1367-80
references.pmid: 21173115
references.citation: Nature. 2006 Jun 15;441(7095):880-4
references.pmid: 16625205
references.citation: Nat Commun. 2014;5:4930
references.pmid: 25222142
references.citation: J Cell Biol. 2005 Oct 10;171(1):87-98
references.pmid: 16203860
references.citation: Autophagy. 2013 Nov 1;9(11):1750-7
references.pmid: 24149988