{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T15:45:11Z","timestamp":1768405511193,"version":"3.49.0"},"reference-count":42,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T00:00:00Z","timestamp":1672790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministero della Salute (Ricerca Corrente 2022)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Cells from glioblastoma multiforme (GBM) feature up-regulation of the mechanistic Target of Rapamycin (mTOR), which brings deleterious effects on malignancy and disease course. At the cellular level, up-regulation of mTOR affects a number of downstream pathways and suppresses autophagy, which is relevant for the neurobiology of GBM. In fact, autophagy acts on several targets, such as protein clearance and mitochondrial status, which are key in promoting the malignancy GBM. A defective protein clearance extends to cellular prion protein (PrPc). Recent evidence indicates that PrPc promotes stemness and alters mitochondrial turnover. Therefore, the present study measures whether in GBM cells abnormal amount of PrPc and mitochondrial alterations are concomitant in baseline conditions and whether they are reverted by mTOR inhibition. Proteins related to mitochondrial turnover were concomitantly assessed. High amounts of PrPc and altered mitochondria were both mitigated dose-dependently by the mTOR inhibitor rapamycin, which produced a persistent activation of the autophagy flux and shifted proliferating cells from S to G1 cell cycle phase. Similarly, mTOR suppression produces a long-lasting increase of proteins promoting mitochondrial turnover, including Pink1\/Parkin. These findings provide novel evidence about the role of autophagy in the neurobiology of GBM.<\/jats:p>","DOI":"10.3390\/cells12020221","type":"journal-article","created":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T01:33:30Z","timestamp":1672882410000},"page":"221","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Autophagy Activation Associates with Suppression of Prion Protein and Improved Mitochondrial Status in Glioblastoma Cells"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4734-8798","authenticated-orcid":false,"given":"Paola","family":"Lenzi","sequence":"first","affiliation":[{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla L.","family":"Busceti","sequence":"additional","affiliation":[{"name":"Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Neuromed, Via Atinense 18, 86077 Pozzilli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gloria","family":"Lazzeri","sequence":"additional","affiliation":[{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8899-0309","authenticated-orcid":false,"given":"Rosangela","family":"Ferese","sequence":"additional","affiliation":[{"name":"Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Neuromed, Via Atinense 18, 86077 Pozzilli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3566-4889","authenticated-orcid":false,"given":"Francesca","family":"Biagioni","sequence":"additional","affiliation":[{"name":"Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Neuromed, Via Atinense 18, 86077 Pozzilli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Salvetti","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 55, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8349-6982","authenticated-orcid":false,"given":"Elena","family":"Pompili","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University of Rome, Via A. Borelli 50, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valerio","family":"De Franchis","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University of Rome, Via A. Borelli 50, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Puglisi-Allegra","sequence":"additional","affiliation":[{"name":"Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Neuromed, Via Atinense 18, 86077 Pozzilli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Frati","sequence":"additional","affiliation":[{"name":"Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) 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