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.

Quantitative ultrastructural morphometry and gene expression of mTOR-related mitochondriogenesis within glioblastoma cells / Ferese, R.; Lenzi, P.; Fulceri, F.; Biagioni, F.; Fabrizi, C.; Gambardella, S.; Familiari, P.; Frati, A.; Limanaqi, F.; Fornai, F.. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1661-6596. - 21:13(2020), pp. 1-35. [10.3390/ijms21134570]

Quantitative ultrastructural morphometry and gene expression of mTOR-related mitochondriogenesis within glioblastoma cells

Fabrizi C.;Familiari P.;Frati A.;
2020

Abstract

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.
2020
Autophagy; Lysosomes; Mitochondrial biogenesis; Mitochondrial constitutive genes; Mitochondrial DNA; Mitophagy; NRF2; PGC1α; Rapamycin
01 Pubblicazione su rivista::01a Articolo in rivista
Quantitative ultrastructural morphometry and gene expression of mTOR-related mitochondriogenesis within glioblastoma cells / Ferese, R.; Lenzi, P.; Fulceri, F.; Biagioni, F.; Fabrizi, C.; Gambardella, S.; Familiari, P.; Frati, A.; Limanaqi, F.; Fornai, F.. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1661-6596. - 21:13(2020), pp. 1-35. [10.3390/ijms21134570]
File allegati a questo prodotto
File Dimensione Formato  
Ferese_Quantitative Ultrastructural Morphometry_2020.pdf

accesso aperto

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Creative commons
Dimensione 1.43 MB
Formato Adobe PDF
1.43 MB Adobe PDF

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1455784
Citazioni
  • ???jsp.display-item.citation.pmc??? 12
  • Scopus 13
  • ???jsp.display-item.citation.isi??? 11
social impact