{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:01:25Z","timestamp":1760148085206,"version":"build-2065373602"},"reference-count":105,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,3,25]],"date-time":"2023-03-25T00:00:00Z","timestamp":1679702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia, I.P.","doi-asserted-by":"publisher","award":["UIDB\/04293\/2020","SFRH\/BD\/136996\/2018","CEECIND\/00724\/2017","CEECIND\/00724\/2017\/CP1386\/CT0006","IF\/00889\/2015","ROTEIRO\/0028\/2013","LISBOA-01-0145-FEDER-022125"],"award-info":[{"award-number":["UIDB\/04293\/2020","SFRH\/BD\/136996\/2018","CEECIND\/00724\/2017","CEECIND\/00724\/2017\/CP1386\/CT0006","IF\/00889\/2015","ROTEIRO\/0028\/2013","LISBOA-01-0145-FEDER-022125"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Portuguese Mass Spectrometry Network, integrated in the National Roadmap of Research Infrastructures of Strategic Relevance","award":["UIDB\/04293\/2020","SFRH\/BD\/136996\/2018","CEECIND\/00724\/2017","CEECIND\/00724\/2017\/CP1386\/CT0006","IF\/00889\/2015","ROTEIRO\/0028\/2013","LISBOA-01-0145-FEDER-022125"],"award-info":[{"award-number":["UIDB\/04293\/2020","SFRH\/BD\/136996\/2018","CEECIND\/00724\/2017","CEECIND\/00724\/2017\/CP1386\/CT0006","IF\/00889\/2015","ROTEIRO\/0028\/2013","LISBOA-01-0145-FEDER-022125"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Niemann\u2013Pick type C1 (NPC1) is an endolysosomal transmembrane protein involved in the export of cholesterol and sphingolipids to other cellular compartments such as the endoplasmic reticulum and plasma membrane. NPC1 loss of function is the major cause of NPC disease, a rare lysosomal storage disorder characterized by an abnormal accumulation of lipids in the late endosomal\/lysosomal network, mitochondrial dysfunction, and impaired autophagy. NPC phenotypes are conserved in yeast lacking Ncr1, an orthologue of human NPC1, leading to premature aging. Herein, we performed a phosphoproteomic analysis to investigate the effect of Ncr1 loss on cellular functions mediated by the yeast lysosome-like vacuoles. Our results revealed changes in vacuolar membrane proteins that are associated mostly with vesicle biology (fusion, transport, organization), autophagy, and ion homeostasis, including iron, manganese, and calcium. Consistently, the cytoplasm to vacuole targeting (Cvt) pathway was increased in ncr1\u2206 cells and autophagy was compromised despite TORC1 inhibition. Moreover, ncr1\u2206 cells exhibited iron overload mediated by the low-iron sensing transcription factor Aft1. Iron deprivation restored the autophagic flux of ncr1\u2206 cells and increased its chronological lifespan and oxidative stress resistance. These results implicate iron overload on autophagy impairment, oxidative stress sensitivity, and cell death in the yeast model of NPC1.<\/jats:p>","DOI":"10.3390\/ijms24076221","type":"journal-article","created":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T04:05:40Z","timestamp":1679889940000},"page":"6221","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Iron Limitation Restores Autophagy and Increases Lifespan in the Yeast Model of Niemann\u2013Pick Type C1"],"prefix":"10.3390","volume":"24","author":[{"given":"Telma S.","family":"Martins","sequence":"first","affiliation":[{"name":"i3S\u2014Instituto de Investigac\u0327\u00e3o e Inovac\u0327\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"IBMC\u2014Instituto de Biologia Molecular e Celular, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"given":"Rafaela S.","family":"Costa","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investigac\u0327\u00e3o e Inovac\u0327\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"IBMC\u2014Instituto de Biologia Molecular e Celular, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9961-0479","authenticated-orcid":false,"given":"Rita","family":"Vila\u00e7a","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investigac\u0327\u00e3o e Inovac\u0327\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"IBMC\u2014Instituto de Biologia Molecular e Celular, Universidade do Porto, 4200-135 Porto, Portugal"}]},{"given":"Carolina","family":"Lemos","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investigac\u0327\u00e3o e Inovac\u0327\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"IBMC\u2014Instituto de Biologia Molecular e Celular, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2179-2946","authenticated-orcid":false,"given":"Vitor","family":"Teixeira","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investigac\u0327\u00e3o e Inovac\u0327\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"IBMC\u2014Instituto de Biologia Molecular e Celular, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8167-6912","authenticated-orcid":false,"given":"Clara","family":"Pereira","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investigac\u0327\u00e3o e Inovac\u0327\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"IBMC\u2014Instituto de Biologia Molecular e Celular, Universidade do Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7868-4663","authenticated-orcid":false,"given":"V\u00edtor","family":"Costa","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investigac\u0327\u00e3o e Inovac\u0327\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"IBMC\u2014Instituto de Biologia Molecular e Celular, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/s41556-018-0244-7","article-title":"The Lysosome as a Cellular Centre for Signalling, Metabolism and Quality Control","volume":"21","author":"Lawrence","year":"2019","journal-title":"Nat. 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