PRESSRELEASE
Takingoutthecellular“trash”–attherightplaceandtherighttime
th
Vienna,October20 ,2016
Newpossibilitiesfortheregulationofmolecularprocesses
NewinsightabouthowcellsdisposeoftheirwasteisnowgivenbythegroupofClaudineKraftatthe
MaxF.PerutzLaboratories(MFPL)oftheUniversityofViennaandtheMedicalUniversityofVienna.They
showthenecessityofaregulationinspaceandtimeofakeyproteininvolvedincellularwastedisposal.
DysfunctionsinthewastedisposalsystemofacellarelinkedtocancerandAlzheimer’sdisease.The
studyispublishedintherenownedjournalMolecularCell.
Acleanapartmentandworkplace,whilecertainlyimportant,arenotstrictlynecessaryinordertosurvive.
Forcells,however,tidyingupisabsolutelyvital.Theresponsibleprocessiscalledautophagy,whichhas
nowbecomewidelyknownduetoYoshinoriOhsumi’swinningoftheNobelPrizeinMedicineinOctober
2016.Duringautophagy,adefinedsetofproteinscoordinatestheremovalofviruses,bacteria,and
damagedorsuperfluousmaterialfromacell.Autophagyalsoenablescellstosurvivetimesofstarvation,by
degradingthecell’sowncomponentstorecycletheirbuildingblocks–similartorecyclingstationsina
town.Thisprocessneedstobetightlycontrolledtopreventtheremovalofstructuresthatarestillrequired
inthecell.“YouwouldnotwanttoaccidentallythrowawayyourTVsetwhilecleaningupyourapartment,
wouldyou?”explainsRaffaelaTorggler,sharedfirstauthorofthestudy.“Foracell,aberrantactivationof
autophagycouldeasilyhavelethalconsequences”.
ThekeyregulatorofautophagyistheproteinAtg1.Itsimportancefortheactivationofautophagyhaslong
beenknowntoresearchers,anddetailsofitsfunctionsweredescribedbytheKraftgroupintheir2014
MolecularCellpublication.However,howAtg1activityandtheprocessofautophagyarecontrolledin
ordertopreventtheiraberrantactivationhadremainedelusive.Now,theteamofClaudineKraftatthe
MFPLoftheUniversityofViennadiscoveredthatAtg1isregulatedinbothspaceandtime.Onlywhen
preciserequirementsaremet,Atg1isactivatedandautophagyisinitiated.
Tostarttheprocess,boththekeyregulatorAtg1aswellasthe“waste”tobediscardedareseparately
broughttothepreciselocationwherethewasteispackedintocellular“garbagebags”.Thesimultaneous
presenceofbothAtg1andthewasteatthisplaceiscrucialfortheactivationofAtg1andtheinitiationof
autophagy.ClaudineKraftandherteamshowedthatthecellallowsAtg1tomeetthewasteonlyatthesite
ofwastepackaging.Thistightlyrestrictsautophagyinitiationinspaceandtimeandpreventsitsaberrant
activation.
InanormalcelltwocoordinatorsbringAtg1andthewasteindependentlyfromeachothertothewaste
packaginglocation.Whenthesecoordinatorsareremovedfromthecell,thewasteandAtg1cannotmeet
andautophagyisnotinduced.DanielPapinski,sharedfirstauthorofthestudy,explains:“Incellswithout
thesecoordinators,wewereabletopromotewasteremovalbyautophagywhenAtg1wasartificially
forcedtomeetthewaste.ThisshowsthattheconcurrenceofAtg1andwasteattherightplaceisakey
regulatorysteptoactivateautophagy".
Thedetailedstudyofsuchfundamentalcellularprocessesiscrucialfortheunderstandingofdiseasesthat
gohandinhandwiththeseevents–inthecaseofautophagy,Alzheimer’sdiseaseorcancer.Inthelong
run,thiswillhelptobettertreatorperhapsevenpreventtheseillnesses.
MAXF.PERUTZLABORATORIES
ViennaBiocenter(VBC,)Dr.Bohr-Gasse9|1030Wien|Austria
Tel:+431427724014
[email protected]|www.mfpl.ac.at
TheMaxF.PerutzLaboratoriesareajointventureof
PRESSRELEASE
ClaudineKraftelaborates:“Thisworkgaveusimportantinsightintothemoleculareventsregulating
autophagyinspaceandtime.Onlyifweunderstandthemoleculardetails,wewillbeabletodesign
medicationexclusivelytargetingautophagyinthesediseases”.
Publicationin"MolecularCell"
TorgglerR,PapinskiD,BrachT,BasL,SchuschnigM,PfaffenwimmerT,RohringerS,MatzholdT,Schweida
D,BrezovichAandKraftC(2016).TwoIndependentPathwayswithinSelectiveAutophagyConvergeto
ActivateAtg1KinaseattheVacuole.MolecularCell,doi:http://dx.doi.org/10.1016/j.molcel.2016.09.008
ScientificContact
Assoc.-Prof.Dr.ClaudineKraft
MaxF.PerutzLaboratories
UniversitätWien
ViennaBiocenter
1030Wien,Dr.-Bohr-Gasse9
T+43-1-4277-52877
M+43-664-60277-52877
[email protected]
PressContact
CaterinaPurini,MSc.
MaxF.PerutzLaboratories
Communications
ViennaBiocenter
1030Wien,Dr.-Bohr-Gasse9
T+43-1-4277-24014
[email protected]
AbouttheMFPL
TheMaxF.PerutzLaboratories(MFPL)areacenterestablishedbytheUniversityofViennaandtheMedical
UniversityofViennatoprovideanenvironmentforexcellent,internationallyrecognizedresearchand
educationinthefieldofMolecularBiology.TheMFPLarelocatedattheViennaBiocenter,oneofthe
largestLifeSciencesclustersinAustria,andhostonaverage60independentresearchgroups,involving
morethan500peoplefrom40nations.
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TheMaxF.PerutzLaboratoriesareajointventureof