CellDeath&Differentiation(2019)26:605–616https://doi.org/10.1038/s41418-018-0252-yREVIEWARTICLEAutophagy-dependentcelldeathDonnaDenton1●SharadKumar1Received:20October2018/Revised:9November2018/Accepted:28November2018/Publishedonline:19December2018©ADMCAssociazioneDifferenziamentoeMorteCellulare2018AbstractAutophagy-dependentcelldeathcanbedefinedascelldemisethathasastrictrequirementofautophagy.Althoughautophagyoftenaccompaniescelldeathfollowingmanytoxicinsults,therequirementofautophagicmachineryforcelldeathexecution,asestablishedthroughspecificgeneticorchemicalinhibitionoftheprocess,ishighlycontextual.Duringanimaldevelopment,perhapsthebestvalidatedmodelofautophagy-dependentcelldeathisthedegradationofthelarvalmidgutduringlarval–pupalmetamorphosis,whereanumberofkeyautophagygenesarerequiredfortheremovalofthetissues.Surprisinglythough,eveninthemidgut,notallofthe‘canonical’autophagicmachineryappearstoberequired.Inotherorganismsandcancercellsmanyvariationsofautophagy-dependentcelldeathareapparent,pointingtothelackofaunifyingcelldeathpathway.Itisthuspossiblethatcomponentsoftheautophagymachineryareselectivelyutilisedorrepurposedforthistypeofcelldeath.Inthisreview,wediscussexamplesofcelldeaththatutiliseautophagymachinery(orpartthereof),thecurrentknowledgeofthecomplexityofautophagy-dependentcellulardemiseandthepotentialmechanismsandregulatorypathwaysinvolvedinsuchcelldeath.Facts●Autophagyoftenaccompaniescelldeath,butautophagy-dependentcelldeathishighlycontextual.●Itutiliseskeycomponentsofthemacroautophagymachinery.●AtleastinDrosophiladevelopment,suchcelldeathishighlyregulated.●Growtharrestoftenprecedesautophagy-dependentcelldeath.Openquestions●Whatarethekeysignalsthatinitiateautophagy-dependentcelldeath?●Whatarethemechanismsofcelldeathdependentonautophagy?●Isthereaunifiedmechanismofautophagy-dependentcelldeath?●Isthemachineryrequiredforautophagyinducedasacellsurvivalresponsethesameasthatmediatingautophagydependentcelldeath?●Howprevalentisautophagy-dependentce...
