PMID- 36672156
OWN - NLM
STAT- MEDLINE
DCOM- 20230124
LR  - 20230212
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 12
IP  - 2
DP  - 2023 Jan 4
TI  - Autophagy Activation Associates with Suppression of Prion Protein and Improved 
      Mitochondrial Status in Glioblastoma Cells.
LID - 10.3390/cells12020221 [doi]
LID - 221
AB  - 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.
FAU - Lenzi, Paola
AU  - Lenzi P
AUID- ORCID: 0000-0002-4734-8798
AD  - Department of Translational Research and New Technologies in Medicine and 
      Surgery, University of Pisa, Via Roma 55, 56126 Pisa, Italy.
FAU - Busceti, Carla L
AU  - Busceti CL
AD  - Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Neuromed, Via 
      Atinense 18, 86077 Pozzilli, Italy.
FAU - Lazzeri, Gloria
AU  - Lazzeri G
AD  - Department of Translational Research and New Technologies in Medicine and 
      Surgery, University of Pisa, Via Roma 55, 56126 Pisa, Italy.
FAU - Ferese, Rosangela
AU  - Ferese R
AUID- ORCID: 0000-0001-8899-0309
AD  - Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Neuromed, Via 
      Atinense 18, 86077 Pozzilli, Italy.
FAU - Biagioni, Francesca
AU  - Biagioni F
AUID- ORCID: 0000-0003-3566-4889
AD  - Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Neuromed, Via 
      Atinense 18, 86077 Pozzilli, Italy.
FAU - Salvetti, Alessandra
AU  - Salvetti A
AD  - Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 
      55, 56126 Pisa, Italy.
FAU - Pompili, Elena
AU  - Pompili E
AUID- ORCID: 0000-0002-8349-6982
AD  - Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza 
      University of Rome, Via A. Borelli 50, 00161 Rome, Italy.
FAU - De Franchis, Valerio
AU  - De Franchis V
AD  - Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza 
      University of Rome, Via A. Borelli 50, 00161 Rome, Italy.
FAU - Puglisi-Allegra, Stefano
AU  - Puglisi-Allegra S
AD  - Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Neuromed, Via 
      Atinense 18, 86077 Pozzilli, Italy.
FAU - Frati, Alessandro
AU  - Frati A
AD  - Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Neuromed, Via 
      Atinense 18, 86077 Pozzilli, Italy.
AD  - Neurosurgery Division, Department of Human Neurosciences, Sapienza University, 
      00135 Roma, Italy.
FAU - Ferrucci, Michela
AU  - Ferrucci M
AD  - Department of Translational Research and New Technologies in Medicine and 
      Surgery, University of Pisa, Via Roma 55, 56126 Pisa, Italy.
FAU - Fornai, Francesco
AU  - Fornai F
AUID- ORCID: 0000-0002-3883-5084
AD  - Department of Translational Research and New Technologies in Medicine and 
      Surgery, University of Pisa, Via Roma 55, 56126 Pisa, Italy.
AD  - Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Neuromed, Via 
      Atinense 18, 86077 Pozzilli, Italy.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230104
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - 0 (Prion Proteins)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Humans
MH  - *Glioblastoma/metabolism
MH  - Prion Proteins/metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Autophagy
MH  - Mitochondria/metabolism
PMC - PMC9857229
OTO - NOTNLM
OT  - DRP1 lysosomes
OT  - Fis1
OT  - Parkin
OT  - Pink1
OT  - cytofluorimetry
OT  - mTOR
OT  - mitochondrial fission
OT  - rapamycin
COIS- The authors declare no conflict of interest.
EDAT- 2023/01/22 06:00
MHDA- 2023/01/25 06:00
PMCR- 2023/01/04
CRDT- 2023/01/21 01:10
PHST- 2022/07/18 00:00 [received]
PHST- 2022/12/23 00:00 [revised]
PHST- 2022/12/24 00:00 [accepted]
PHST- 2023/01/21 01:10 [entrez]
PHST- 2023/01/22 06:00 [pubmed]
PHST- 2023/01/25 06:00 [medline]
PHST- 2023/01/04 00:00 [pmc-release]
AID - cells12020221 [pii]
AID - cells-12-00221 [pii]
AID - 10.3390/cells12020221 [doi]
PST - epublish
SO  - Cells. 2023 Jan 4;12(2):221. doi: 10.3390/cells12020221.