K-ras transformed fibroblasts have been shown to have a stronger dependence from glycolysis, reduced oxidative phosphorylation ability and a fragility towards glucose depletion compared to their immortalized, normal counterparts. In this paper, using RNA profiling assays and metabolic perturbations, we report changes in expression of genes encoding mitochondrial proteins and alterations in mitochondrial morphology that correlate with mitochondrial functionality. In fact, unlike normal cells, transformed cells show reduced ATP content and inability to modify mitochondria morphology upon glucose depletion. Being reverted by GEF-DN expression, such morphological and functional changes are directly connected to Ras activation. Taken together with reported partial mitochondrial uncoupling and more sustained apoptosis of transformed cells, our results indicate that activation of the Ras pathway strikingly impacts on energy and signaling-related aspects of mitochondria functionality, that in turn may affect the terminal phenotype of transformed cells. © 2006 Elsevier B.V. All rights reserved.

Chiaradonna, F., Gaglio, D., Vanoni, M., Alberghina, L. (2006). Expression of transforming K-Ras oncogene affects mitochondrial function and morphology in mouse fibroblasts. BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS, 1757(9-10), 1338-1356 [10.1016/j.bbabio.2006.08.001].

Expression of transforming K-Ras oncogene affects mitochondrial function and morphology in mouse fibroblasts

CHIARADONNA, FERDINANDO;GAGLIO, DANIELA;VANONI, MARCO ERCOLE;ALBERGHINA, LILIA
2006

Abstract

K-ras transformed fibroblasts have been shown to have a stronger dependence from glycolysis, reduced oxidative phosphorylation ability and a fragility towards glucose depletion compared to their immortalized, normal counterparts. In this paper, using RNA profiling assays and metabolic perturbations, we report changes in expression of genes encoding mitochondrial proteins and alterations in mitochondrial morphology that correlate with mitochondrial functionality. In fact, unlike normal cells, transformed cells show reduced ATP content and inability to modify mitochondria morphology upon glucose depletion. Being reverted by GEF-DN expression, such morphological and functional changes are directly connected to Ras activation. Taken together with reported partial mitochondrial uncoupling and more sustained apoptosis of transformed cells, our results indicate that activation of the Ras pathway strikingly impacts on energy and signaling-related aspects of mitochondria functionality, that in turn may affect the terminal phenotype of transformed cells. © 2006 Elsevier B.V. All rights reserved.
Articolo in rivista - Articolo scientifico
K-Ras oncogene, mouse fibroblasts
English
2006
1757
9-10
1338
1356
none
Chiaradonna, F., Gaglio, D., Vanoni, M., Alberghina, L. (2006). Expression of transforming K-Ras oncogene affects mitochondrial function and morphology in mouse fibroblasts. BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS, 1757(9-10), 1338-1356 [10.1016/j.bbabio.2006.08.001].
File in questo prodotto:
Non ci sono file associati a questo prodotto.

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/10281/3655
Citazioni
  • Scopus 68
  • ???jsp.display-item.citation.isi??? 63
Social impact