PMID- 32604996
OWN - NLM
STAT- MEDLINE
DCOM- 20210215
LR  - 20211204
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 21
IP  - 13
DP  - 2020 Jun 27
TI  - Quantitative Ultrastructural Morphometry and Gene Expression of mTOR-Related 
      Mitochondriogenesis within Glioblastoma Cells.
LID - 10.3390/ijms21134570 [doi]
LID - 4570
AB  - In glioblastoma (GBM) cells, an impairment of mitochondrial activity along with 
      autophagy suppression occurs. Autophagy suppression in GBM promotes stemness, 
      invasion, and poor prognosis. The autophagy deficit seems to be due, at least in 
      part, to an abnormal up-regulation of the mammalian target of rapamycin (mTOR), 
      which may be counteracted by pharmacological mTORC1 inhibition. Since autophagy 
      activation is tightly bound to increased mitochondriogenesis, a defect in the 
      synthesis of novel mitochondria is expected to occur in GBM cells. In an effort 
      to measure a baseline deficit in mitochondria and promote mitochondriogenesis, 
      the present study used two different GBM cell lines, both featuring mTOR 
      hyperactivity. mTORC1 inhibition increases the expression of genes and proteins 
      related to autophagy, mitophagy, and mitochondriogenesis. Autophagy activation 
      was counted by RT-PCR of autophagy genes, LC3- immune-fluorescent puncta and 
      immune-gold, as well as specific mitophagy-dependent BNIP3 stoichiometric 
      increase in situ, within mitochondria. The activation of autophagy-related 
      molecules and organelles after rapamycin exposure occurs concomitantly with 
      progression of autophagosomes towards lysosomes. Remarkably, mitochondrial 
      biogenesis and plasticity (increased mitochondrial number, integrity, and density 
      as well as decreased mitochondrial area) was long- lasting for weeks 
      following rapamycin withdrawal.
FAU - Ferese, Rosangela
AU  - Ferese R
AD  - I.R.C.C.S. Neuromed, via Atinense 18, 86077 Pozzilli (IS), Italy.
FAU - Lenzi, Paola
AU  - Lenzi P
AD  - Department of Translational Research and New Technologies in Medicine and 
      Surgery, University of Pisa, via Roma 55, 56126 Pisa, Italy.
FAU - Fulceri, Federica
AU  - Fulceri F
AD  - Department of Clinical and Experimental Medicine University of Pisa, via Roma 55, 
      56126 Pisa, Italy.
FAU - Biagioni, Francesca
AU  - Biagioni F
AUID- ORCID: 0000-0003-3566-4889
AD  - I.R.C.C.S. Neuromed, via Atinense 18, 86077 Pozzilli (IS), Italy.
FAU - Fabrizi, Cinzia
AU  - Fabrizi C
AUID- ORCID: 0000-0002-6007-754X
AD  - Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza 
      University of Rome, Via A. Borelli 50, 00161 Rome, Italy.
FAU - Gambardella, Stefano
AU  - Gambardella S
AD  - I.R.C.C.S. Neuromed, via Atinense 18, 86077 Pozzilli (IS), Italy.
AD  - Department of Biomolecular Sciences, University of Urbino "Carlo Bo", 61029 
      Urbino, Italy.
FAU - Familiari, Pietro
AU  - Familiari P
AUID- ORCID: 0000-0003-0513-2312
AD  - Department of Human Neurosciences, Division of Neurosurgery, Sapienza University 
      of Rome, 00185 Roma, Italy.
FAU - Frati, Alessandro
AU  - Frati A
AD  - I.R.C.C.S. Neuromed, via Atinense 18, 86077 Pozzilli (IS), Italy.
FAU - Limanaqi, Fiona
AU  - Limanaqi F
AUID- ORCID: 0000-0003-0185-2099
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  - I.R.C.C.S. Neuromed, via Atinense 18, 86077 Pozzilli (IS), Italy.
AD  - Department of Translational Research and New Technologies in Medicine and 
      Surgery, University of Pisa, via Roma 55, 56126 Pisa, Italy.
LA  - eng
GR  - Ricerca Corrente 2020/Ministero della Salute/
PT  - Journal Article
DEP - 20200627
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Reactive Oxygen Species)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - *Gene Expression Regulation, Neoplastic
MH  - Glioblastoma/genetics/metabolism/*pathology
MH  - Humans
MH  - Mitochondria/genetics/metabolism/*pathology
MH  - *Mitophagy
MH  - *Organelle Biogenesis
MH  - Reactive Oxygen Species/metabolism
MH  - TOR Serine-Threonine Kinases/genetics/*metabolism
MH  - Tumor Cells, Cultured
PMC - PMC7370179
OTO - NOTNLM
OT  - NRF2
OT  - PGC1
OT  - autophagy
OT  - lysosomes
OT  - mitochondrial DNA
OT  - mitochondrial biogenesis
OT  - mitochondrial constitutive genes
OT  - mitophagy
OT  - rapamycin
COIS- The authors declare no conflict of interest.
EDAT- 2020/07/02 06:00
MHDA- 2021/02/16 06:00
PMCR- 2020/07/01
CRDT- 2020/07/02 06:00
PHST- 2020/04/30 00:00 [received]
PHST- 2020/06/22 00:00 [revised]
PHST- 2020/06/26 00:00 [accepted]
PHST- 2020/07/02 06:00 [entrez]
PHST- 2020/07/02 06:00 [pubmed]
PHST- 2021/02/16 06:00 [medline]
PHST- 2020/07/01 00:00 [pmc-release]
AID - ijms21134570 [pii]
AID - ijms-21-04570 [pii]
AID - 10.3390/ijms21134570 [doi]
PST - epublish
SO  - Int J Mol Sci. 2020 Jun 27;21(13):4570. doi: 10.3390/ijms21134570.