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The Insulin-like Growth Factor-I–mTOR Signaling Pathway Induces the Mitochondrial Pyrimidine Nucleotide Carrier to Promote Cell Growth
- 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.
- Subjects :
- medicine.medical_treatment
Molecular Sequence Data
Uridine Triphosphate
Mitochondrion
Biology
Receptor, IGF Type 1
Mitochondrial Proteins
Mice
Cell Line, Tumor
medicine
Animals
Humans
Insulin
Amino Acid Sequence
Insulin-Like Growth Factor I
RNA, Small Interfering
Molecular Biology
Protein kinase B
PI3K/AKT/mTOR pathway
Cell Line, Transformed
Cell Proliferation
Cell Size
RECEPTOR
IDENTIFICATION
Cell growth
TOR Serine-Threonine Kinases
Growth factor
TRANSPORTER
RPTOR
Biological Transport
Articles
Cell Biology
Fibroblasts
Mitochondrial carrier
CANCER
GENE
Mitochondria
Cell biology
Enzyme Activation
Gene Expression Regulation, Neoplastic
Nucleotide Transport Proteins
Signal transduction
Reactive Oxygen Species
Protein Kinases
Signal Transduction
Subjects
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