Lysosomes: Biology, Diseases, and Therapeutics

562 Pages·2015·6.585 MB·English

by  Maxfield, Frederick;Willard, James;Lu, Shuyan

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LYSOSOMES
Biology, Diseases, and Therapeutics
Edited by
FREDERICKR.MAXFIELD
JAMESM.WILLARD
SHUYANLU
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LibraryofCongressCataloging-in-PublicationData:
Names:Maxfield,FrederickR.,editor.|Willard,JamesM.,1955-,editor.|
Lu,Shuyan,1971-,editor.
Title:Lysosomes:biology,diseases,andtherapeutics/editedbyFrederick
R.Maxfield,JamesM.Willard,ShuyanLu.
Othertitles:Lysosomes(Maxfield)
Description:Hoboken,NewJersey:JohnWiley&Sons,Inc.,[2016]|Includes
bibliographicalreferencesandindex.
Identifiers:LCCN2016006834(print)|LCCN2016008790(ebook)|ISBN
9781118645154(cloth)|ISBN9781118978306(pdf)|ISBN9781118978313
(epub)
Subjects:|MESH:Lysosomes
Classification:LCCQH603.L9(print)|LCCQH603.L9(ebook)|NLMQU350|
DDC571.6/55–dc23
LCrecordavailableathttps://lccn.loc.gov/2016006834
PrintedintheUnitedStatesofAmerica
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CONTENTS
PREFACE xiii
(cid:2) LISTOFCONTRIBUTORS xvii (cid:2)
1 Lysosomes:AnIntroduction 1
FrederickR.Maxfield
1.1 HistoricalBackground, 2
References, 4
2 LysosomeBiogenesisandAutophagy 7
FulvioReggioriandJudithKlumperman
2.1 Introduction, 7
2.2 PathwaystotheLysosomes, 10
2.2.1 BiosyntheticTransportRoutestotheLysosome, 10
2.2.2 EndocyticPathwaystotheLysosome, 10
2.2.3 AutophagyPathwaystotheLysosome, 12
2.2.4 TheATGProteins:TheKeyRegulatorsofAutophagy, 14
2.3 FusionandFissionbetweentheEndolysosomalandAutophagy
Pathways, 16
2.3.1 RecyclingEndosomesandAutophagosomeBiogenesis, 16
2.3.2 AutophagosomeFusionwithLateEndosomesand
Lysosomes, 17
2.3.3 AutophagicLysosomalReformation, 18
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iv CONTENTS
2.4 Diseases, 19
2.4.1 Lysosome-RelatedDisorders(LSDs), 19
2.4.2 LysosomesinNeurodegenerationandItsLinks
toAutophagy, 20
2.4.3 Autophagy-RelatedDiseases, 20
2.5 ConcludingRemarks, 22
Acknowledgments, 23
References, 23
3 MultivesicularBodies:RolesinIntracellularandIntercellular
Signaling 33
EmilyR.Eden,ThomasBurgoyne,andClareE.Futter
3.1 Introduction, 33
3.2 DownregulationofSignalingbySortingontoILVs, 35
3.3 UpregulationofSignalingbySortingontoILVs, 38
3.4 IntercellularSignalingDependentonSortingontoILVs, 39
3.5 Conclusion, 44
References, 45
4 LysosomesandMitophagy 51
DominikHaddadandPatrikVerstreken
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4.1 Summary, 51
4.2 MitochondrialSignificance, 51
4.3 HistoryofMitophagy, 52
4.4 MechanismsofMitophagy, 53
4.4.1 MitophagyinYeast, 54
4.4.2 MitophagyinMammals, 55
4.5 Conclusion, 57
Acknowledgments, 57
References, 58
5 LysosomeExocytosisandMembraneRepair 63
RajeshK.SinghandAbigailS.Haka
5.1 Introduction, 63
5.2 FunctionsofLysosomeExocytosis, 63
5.2.1 SpecializedLysosome-RelatedOrganelles, 64
5.2.2 LysosomeExocytosisforMembraneRepair, 65
5.2.3 LysosomeExocytosisasaSourceofMembrane, 66
5.2.4 LysosomeExocytosisforExtracellularDegradation, 66
5.2.5 LysosomeExocytosisandDeliveryofProteinstotheCell
Surface, 68
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CONTENTS v
5.3 MechanismsofLysosomeExocytosis, 68
5.3.1 MaturationofLysosomesandLysosome-Related
Organelles, 69
5.3.2 TransportofLysosomestothePlasmaMembrane, 70
5.3.3 TetheringofLysosomestothePlasmaMembrane, 72
5.3.4 LysosomeFusionwiththePlasmaMembrane, 75
5.3.5 Calcium-DependentExocytosis, 76
5.4 Conclusion, 76
Acknowledgments, 77
References, 77
6 RoleofLysosomesinLipidMetabolism 87
FrederickR.Maxfield
6.1 Introduction, 87
6.2 EndocyticUptakeofLipoproteins, 88
6.3 LipidMetabolisminLateEndosomesandLysosomes, 91
6.4 AutophagyandLysosomalLipidTurnover, 94
6.5 LysosomalLipidHydrolysisandMetabolicRegulation, 95
6.6 Summary, 96
References, 96
(cid:2) 7 TFEB,MasterRegulatorofCellularClearance 101 (cid:2)
GracianaDiez-RouxandAndreaBallabio
7.1 Lysosome, 101
7.2 TheTranscriptionalRegulationofLysosomalFunction, 102
7.3 TFEBSubcellularRegulationisRegulatedbyItsPhosphorylation, 104
7.4 ALysosome-to-NucleusSignalingMechanism, 105
7.5 TFEBandCellularClearanceinHumanDisease, 106
7.5.1 LysosomalStorageDisorders, 107
7.5.2 NeurodegenerativeDisorders, 109
7.5.3 MetabolicSyndrome, 110
7.5.4 Cancer,InbornErrorsofMetabolism,Immunity,
andLongevity, 110
References, 111
8 LysosomalMembranePermeabilizationinCellDeath 115
UrškaRepnikandBorisTurk
8.1 Introduction, 115
8.2 CellDeathModalities, 116
8.3 LysosomalMembranePermeabilization(LMP)andCellDeath, 117
8.3.1 MechanismsofLMP, 118
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8.3.2 UpstreamofLMP:DirectInsultVersusMolecular
Signaling, 121
8.3.3 SignalingDownstreamofLMP, 124
8.4 Conclusion, 127
Acknowledgments, 127
References, 128
9 TheLysosomeinAging-RelatedNeurodegenerativeDiseases 137
RalphA.Nixon
9.1 Introduction, 137
9.2 LysosomeFunctioninAgingOrganisms, 139
9.3 LysosomesandDiseasesofLateAgeOnset, 142
9.3.1 CardiovascularDisease, 142
9.4 LysosomesinAging-RelatedNeurodegenerativeDiseases, 144
9.4.1 Alzheimer’sDisease(AD), 145
9.4.2 Parkinson’sDiseaseandRelatedDisorders, 150
9.4.3 DiffuseLewyBodyDisease(DLB), 155
9.4.4 FrontotemporalLobarDegeneration(FTLD), 155
9.5 Conclusion, 158
Acknowledgments, 158
References, 159
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10 LysosomeandCancer 181
MarjaJäätteläandTuulaKallunki
10.1 Introduction, 181
10.2 LysosomalFunctionandItsImportanceforCancerDevelopment
andProgression, 181
10.3 Cancer-InducedChangesinLysosomalFunction, 182
10.3.1 IncreasedActivityofLysosomalEnzymes, 182
10.3.2 AlteredLysosomeMembranePermeability, 184
10.3.3 IncreasedLysosomeSize, 184
10.3.4 AlteredLysosomeTrafficking – IncreasedLysosomal
Exocytosis, 185
10.4 Cancer-InducedChangesinLysosomeComposition, 185
10.4.1 ChangesinLysosomalHydrolases, 185
10.4.2 ChangesintheLysosomalMembraneProteins, 192
10.5 MolecularChangesInvolvingLysosomalIntegrity, 193
10.5.1 Cancer-AssociatedChangesinLysosomalSphingolipid
Metabolism, 193
10.5.2 TargetingLysosomalMembraneIntegrity, 195
10.6 Conclusion, 196
References, 197
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CONTENTS vii
11 TheGeneticsofSphingolipidHydrolasesandSphingolipidStorage
Diseases 209
EdwardH.SchuchmanandCalogeraM.Simonaro
11.1 IntroductionandOverview, 209
11.2 AcidCeramidaseDeficiency:FarberDisease, 210
11.3 AcidSphingomyelinaseDeficiency:TypesAandBNiemann–Pick
Disease, 213
11.4 Beta-GlucocerebrosidaseDeficiency:GaucherDisease, 215
11.5 GalactocerebrosidaseDeficiency:KrabbeDisease/GloboidCell
Leukodystrophy, 218
11.6 ArylsulfataseaDeficiency:MetachromaticLeukodystrophy, 219
11.7 Alpha-GalactosidaseaDeficiency:FabryDisease, 221
11.8 Beta-GalactosidaseDeficiency:GM1Gangliosidosis, 224
11.9 HexosaminidaseAandBDeficiency:GM2Gangliosidoses, 226
11.10SphingolipidActivatorProteins, 229
References, 231
12 Lysosome-RelatedOrganelles:ModificationsoftheLysosome
Paradigm 239
AdrianaR.MantegazzaandMichaelS.Marks
(cid:2) 12.1 DifferencesBetweenLROsandSecretoryGranules, 240 (cid:2)
12.2 PhysiologicalFunctionsofLROs, 240
12.3 LROBiogenesis, 244
12.3.1 Chediak–HigashiSyndromeandGrayPlatelet
Syndrome, 244
12.3.2 Hermansky–PudlakSyndrome, 246
12.3.3 MelanosomeBiogenesis, 247
12.3.4 HPSandMelanosomeMaturation, 248
12.3.5 HPSandtheBiogenesisofOtherLROs, 250
12.3.6 HPSandNeurosecretoryGranuleBiogenesis, 250
12.3.7 Weibel–PaladeBodyBiogenesis, 251
12.4 LROMotility,Docking,andSecretion, 252
12.5 LROsandImmunitytoPathogens, 253
12.5.1 CytolyticGranules, 253
12.5.2 FamilialHemophagocyticLymphohistiocytosisandCytolytic
GranuleSecretion, 254
12.5.3 AzurophilicGranules, 255
12.5.4 NADPHOxidase-ContainingLROs, 255
12.5.5 IRF7-SignalingLROsandTypeIInterferonInduction, 256
12.5.6 MIICs:LROsorConventionalLate
Endosome/Lysosomes?, 256
12.5.7 PhagosomesandAutophagosomesasNewCandidate
LROs, 258
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12.6 Perspectives, 260
Acknowledgments, 260
References, 260
13 AutophagyInhibitionasaStrategyforCancerTherapy 279
XiaohongMa,ShengfuPiao,QuentinMcafee, andRaviK.Amaravadi
13.1 StagesandStepsofAutophagy, 282
13.2 InductionofAutophagy, 283
13.3 StudiesinMouseModelsUnraveltheDualRolesofAutophagy
inTumorBiology, 285
13.4 ClinicalStudiesonAutophagy’sDualRoleinTumorigenesis, 286
13.5 MouseModelsProvidetheRationaleforAutophagyModulationinthe
ContextofCancerTherapy, 288
13.6 MultipleDruggableTargetsintheAutophagyPathway, 291
13.7 OverviewofPreclinicalAutophagyInhibitorsandEvidenceSupporting
CombinationwithExistingandNewAnticancerAgents, 292
13.8 ProximalAutophagyInhibitors, 293
13.9 Quinolines:FromAntimalarialstoPrototypicalDistalAutophagy
Inhibitors, 293
13.10SummaryfortheClinicalTrialsforCQ/HCQ, 295
13.11DevelopingMorePotentAnticancerAutophagyInhibitors, 298
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13.12Summary,Conclusion,andFutureDirections, 300
13.13InSummary, 302
References, 302
14 AutophagyEnhancers,arewethereYet? 315
ShuyanLuandRalphA.Nixon
14.1 Introduction, 315
14.2 AutophagyImpairmentandDiseases, 316
14.3 AutophagyEnhancerScreening, 317
14.3.1 MethodsforMonitoringAutophagy, 317
14.3.2 AutophagyEnhancersIdentifiedfromEarlyLiterature, 326
14.3.3 mTORInhibitors, 331
14.4 OtherAgentsthatBoostAutophagyandLysosomalFunctions, 335
14.4.1 HDACInhibition, 336
14.4.2 pHRestoration, 337
14.4.3 TRPActivator, 337
14.4.4 TFEBOverexpression/Activation, 338
14.4.5 LysosomalEfficiency, 338
14.4.6 MicroRNA, 339
14.5 ConcludingRemarks, 340
References, 341
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