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AutophagypreventsautophagiccelldeathinTetrahymenainresponsetooxidativestress

, PP. 167-173

Keywords: Autophagy,Autophagiccelldeath,Lysosome,Mitochondria,Reactiveoxygenspecies,Tetrahymena

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Abstract:

Autophagyisamajorcellularpathwayusedtodegradelong-livedproteinsororganellesthatmaybedamagedduetoincreasedreactiveoxygenspecies(ROS)generatedbycellularstress.Autophagytypicallyenhancescellsurvival,butitmayalsoacttopromotecelldeathundercertainconditions.Themechanismunderlyingthisparadox,however,remainsunclear.WeshowedthatTetrahymenacellsexertedincreasedmembrane-boundvacuolescharacteristicofautophagyfollowedbyautophagiccelldeath(referredtoascelldeathwithautophagy)afterexposuretohydrogenperoxide.Inhibitionofautophagybychloroquineor3-methyladeninesignificantlyaugmentedautophagiccelldeathinducedbyhydrogenperoxide.BlockageofthemitochondrialelectrontransportchainorstarvationtriggeredactivationofautophagyfollowedbycelldeathbyinducingtheproductionofROSduetothelossofmitochondrialmembranepotential.ThisindicatedaregulatoryroleofmitochondrialROSinprogrammingautophagyandautophagiccelldeathinTetrahymena.Importantly,suppressionofautophagyenhancedautophagiccelldeathinTetrahymenainresponsetoelevatedROSproductionfromstarvation,andthiswasreversedbyantioxidants.Therefore,ourresultssuggestthatautophagywasactivateduponoxidativestresstopreventtheinitiationofautophagiccelldeathinTetrahymenauntiltheaccumulationofROSpassedthepointofnoreturn,leadingtodelayedcelldeathinTetrahymena.

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