OXPHOS dysfunction regulates integrin-beta 1 modifications and enhances cell motility and migration

• Type: Article in International Scientific Journal
• Date: 2015

Authors

Joana B Nunes (Author) Other; Joana Peixoto (Author) Other; Paula Soares (Author) FMUP; Valdemar Maximo (Author) Other; Sandra Carvalho (Author) Other; Salome S Pinho (Author) Other; Andre F Vieira (Author) Other; Joana Paredes (Author) Other; Ana C Rego (Author) Other; Ildete L Ferreira (Author) Other; Maria Gomez Lazaro (Author) Other; Manuel Sobrinho Simoes (Author) Other; Keshav K Singh (Author) Other; Jorge Lima (Author) Other

Journal

Title: Human Molecular Genetics

Vol. 24

Pages: 1977-1990

ISSN: 0964-6906

Publisher: Oxford University Press

Indexing

ISI Web of Knowledge - 34 Citations

Scopus - 35 Citations

Scientific classification

FOS: Natural sciences > Biological sciences

Other information

Authenticus ID: P-00A-BD6

DOI: 10.1093/hmg/ddu612

Abstract (EN): Mitochondria are central organelles for cellular metabolism. In cancer cells, mitochondrial oxidative phosphorylation (OXPHOS) dysfunction has been shown to promote migration, invasion, metastization and apoptosis resistance. With the purpose of analysing the effects of OXPHOS dysfunction in cancer cells and the molecular players involved, we generated cybrid cell lines harbouring either wild-type (WT) or mutant mitochondrial DNA (mtDNA) [tRNAmut cybrids, which harbour the pathogenic A3243T mutation in the leucine transfer RNA gene (tRNAleu)]. tRNAmut cybrids exhibited lower oxygen consumption and higher glucose consumption and lactate production than WT cybrids. tRNAmut cybrids displayed increased motility and migration capacities, which were associated with altered integrin-beta 1 N-glycosylation, in particular with higher levels of beta-1,6-N-acetylglucosamine (GlcNAc) branched N-glycans. This integrin-beta 1 N-glycosylation pattern was correlated with higher levels of membrane-bound integrin-beta 1 and also with increased binding to fibronectin. When cultured in vitro, tRNAmut cybrids presented lower growth rate than WT cybrids, however, when injected in nude mice, tRNAmut cybrids produced larger tumours and showed higher metastatic potential than WT cybrids. We conclude that mtDNA-driven OXPHOS dysfunction correlates with increased motility and migration capacities, through a mechanism that may involve the cross talk between cancer cell mitochondria and the extracellular matrix.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 14