Back to Search Start Over

The Insulin-like Growth Factor-I–mTOR Signaling Pathway Induces the Mitochondrial Pyrimidine Nucleotide Carrier to Promote Cell Growth

Authors :
Edmund R.S. Kunji
Dirk Jan Slotboom
Rosemary O'Connor
Giuseppe Trigiante
Suzanne Floyd
Ferdinando Palmieri
Cedric Favre
Gary Loughran
Madeline Leahy
Alexander Marx
Francesco M. Lasorsa
Katie O'Callaghan
Carlo M.T. Marobbio
Philipp Stroebel
Source :
Molecular biology of the cell 18 (2007): 3545–3555. doi:10.1091/mbc.E06-12-1109, info:cnr-pdr/source/autori:Floyd S, Favre C, Lasorsa FM, Leahy M, Trigiante G, Stroebel P, Marx A, Loughran G, O'Callaghan K, Marobbio CM, Slotboom DJ, Kunji ER, Palmieri F, O'Connor R./titolo:The insulin-like growth factor-I-mTOR signaling pathway induces the mitochondrial pyrimidine nucleotide carrier to promote cell growth./doi:10.1091%2Fmbc.E06-12-1109/rivista:Molecular biology of the cell/anno:2007/pagina_da:3545/pagina_a:3555/intervallo_pagine:3545–3555/volume:18
Publication Year :
2007
Publisher :
American Society for Cell Biology (ASCB), 2007.

Abstract

The insulin/insulin-like growth factor (IGF) signaling pathway to mTOR is essential for the survival and growth of normal cells and also contributes to the genesis and progression of cancer. This signaling pathway is linked with regulation of mitochondrial function, but how is incompletely understood. Here we show that IGF-I and insulin induce rapid transcription of the mitochondrial pyrimidine nucleotide carrier PNC1, which shares significant identity with the essential yeast mitochondrial carrier Rim2p. PNC1 expression is dependent on PI-3 kinase and mTOR activity and is higher in transformed fibroblasts, cancer cell lines, and primary prostate cancers than in normal tissues. Overexpression of PNC1 enhances cell size, whereas suppression of PNC1 expression causes reduced cell size and retarded cell cycle progression and proliferation. Cells with reduced PNC1 expression have reduced mitochondrial UTP levels, but while mitochondrial membrane potential and cellular ATP are not altered, cellular ROS levels are increased. Overall the data indicate that PNC1 is a target of the IGF-I/mTOR pathway that is essential for mitochondrial activity in regulating cell growth and proliferation.

Details

ISSN :
19394586 and 10591524
Volume :
18
Database :
OpenAIRE
Journal :
Molecular Biology of the Cell
Accession number :
edsair.doi.dedup.....53ea62a774407842fcc1f05c8c2b2fa6
Full Text :
https://doi.org/10.1091/mbc.e06-12-1109