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http://purl.uniprot.org/citations/25327288http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/25327288http://www.w3.org/2000/01/rdf-schema#comment"Cells rely on autophagy to clear misfolded proteins and damaged organelles to maintain cellular homeostasis. In this study we use the new autophagy inhibitor PIK-III to screen for autophagy substrates. PIK-III is a selective inhibitor of VPS34 that binds a unique hydrophobic pocket not present in related kinases such as PI(3)Kα. PIK-III acutely inhibits autophagy and de novo lipidation of LC3, and leads to the stabilization of autophagy substrates. By performing ubiquitin-affinity proteomics on PIK-III-treated cells we identified substrates including NCOA4, which accumulates in ATG7-deficient cells and co-localizes with autolysosomes. NCOA4 directly binds ferritin heavy chain-1 (FTH1) to target the iron-binding ferritin complex with a relative molecular mass of 450,000 to autolysosomes following starvation or iron depletion. Interestingly, Ncoa4(-/-) mice exhibit a profound accumulation of iron in splenic macrophages, which are critical for the reutilization of iron from engulfed red blood cells. Taken together, the results of this study provide a new mechanism for selective autophagy of ferritin and reveal a previously unappreciated role for autophagy and NCOA4 in the control of iron homeostasis in vivo."xsd:string
http://purl.uniprot.org/citations/25327288http://purl.org/dc/terms/identifier"doi:10.1038/ncb3053"xsd:string
http://purl.uniprot.org/citations/25327288http://purl.uniprot.org/core/author"Fang Q."xsd:string
http://purl.uniprot.org/citations/25327288http://purl.uniprot.org/core/author"Liu S."xsd:string
http://purl.uniprot.org/citations/25327288http://purl.uniprot.org/core/author"Lei H."xsd:string
http://purl.uniprot.org/citations/25327288http://purl.uniprot.org/core/author"Mao X."xsd:string
http://purl.uniprot.org/citations/25327288http://purl.uniprot.org/core/author"Wang Z."xsd:string
http://purl.uniprot.org/citations/25327288http://purl.uniprot.org/core/author"Wang H."xsd:string
http://purl.uniprot.org/citations/25327288http://purl.uniprot.org/core/author"Thomas J."xsd:string
http://purl.uniprot.org/citations/25327288http://purl.uniprot.org/core/author"Menon S."xsd:string
http://purl.uniprot.org/citations/25327288http://purl.uniprot.org/core/author"Porter J.A."xsd:string
http://purl.uniprot.org/citations/25327288http://purl.uniprot.org/core/author"Wilson C.J."xsd:string
http://purl.uniprot.org/citations/25327288http://purl.uniprot.org/core/author"Elling R.A."xsd:string
http://purl.uniprot.org/citations/25327288http://purl.uniprot.org/core/author"Honda A."xsd:string
http://purl.uniprot.org/citations/25327288http://purl.uniprot.org/core/author"Schirle M."xsd:string
http://purl.uniprot.org/citations/25327288http://purl.uniprot.org/core/author"Nagel J."xsd:string
http://purl.uniprot.org/citations/25327288http://purl.uniprot.org/core/author"Powers A.F."xsd:string
http://purl.uniprot.org/citations/25327288http://purl.uniprot.org/core/author"Manning B.D."xsd:string
http://purl.uniprot.org/citations/25327288http://purl.uniprot.org/core/author"Hamann L.G."xsd:string
http://purl.uniprot.org/citations/25327288http://purl.uniprot.org/core/author"Helliwell S.B."xsd:string
http://purl.uniprot.org/citations/25327288http://purl.uniprot.org/core/author"Bussiere D.E."xsd:string
http://purl.uniprot.org/citations/25327288http://purl.uniprot.org/core/author"Nicholson T."xsd:string
http://purl.uniprot.org/citations/25327288http://purl.uniprot.org/core/author"Labow M.A."xsd:string
http://purl.uniprot.org/citations/25327288http://purl.uniprot.org/core/author"Burdick D."xsd:string