Type

Journal Article

Authors

R O'Connor
D Papkovsky
M Leahy
A Zhdanov
C Favre

Subjects

Biochemistry

Topics
neoplasms cell nucleus reactive oxygen species mitochondrial proteins map kinase signaling system pnc1 protein human humans rna small interfering nucleotide transport proteins hela cells genetics metabolism dna mitochondrial adenosine triphosphate biosynthesis deficiency gene expression regulation neoplastic pathology phenotype mesoderm cell respiration mitochondria glycolysis epithelial cells dna replication neoplasm invasiveness animals

Mitochondrial pyrimidine nucleotide carrier (PNC1) regulates mitochondrial biogenesis and the invasive phenotype of cancer cells. (2010)

Abstract The insulin-like growth factor (IGF-I) signalling pathway is essential for metabolism, cell growth and survival. It induces expression of the mitochondrial pyrimidine nucleotide carrier 1 (PNC1) in transformed cells, but the consequences of this for cell phenotype are unknown. Here we show that PNC1 is necessary to maintain mitochondrial function by controlling mitochondrial DNA replication and the ratio of transcription of mitochondrial genes relative to nuclear genes. PNC1 suppression causes reduced oxidative phosphorylation and leakage of reactive oxygen species (ROS), which activates the AMPK-PGC1alpha signalling pathway and promotes mitochondrial biogenesis. Overexpression of PNC1 suppresses mitochondrial biogenesis. Suppression of PNC1 causes a profound ROS-dependent epithelial-mesenchymal transition (EMT), whereas overexpression of PNC1 suppresses both basal EMT and induction of EMT by TGF-beta. Overall, our findings indicate that PNC1 is essential for mitochondria maintenance and suggest that its induction by IGF-I facilitates cell growth whereas protecting cells from an ROS-promoted differentiation programme that arises from mitochondrial dysfunction.
Collections Ireland -> University College Cork -> PubMed

Full list of authors on original publication

R O'Connor, D Papkovsky, M Leahy, A Zhdanov, C Favre

Experts in our system

1
Robert O'Connor
Dublin City University
Total Publications: 74
 
2
Dmitri B Papkovsky
University College Cork
Total Publications: 89
 
3
Martin J. Leahy
National University of Ireland Galway
Total Publications: 39
 
4
Alexander V Zhdanov
University College Cork
Total Publications: 37
 
5
C Favre
University College Cork
Total Publications: 4