Impact on oxidative phosphorylation of immortalization with the telomerase gene

Abstract Skin fibroblasts are essential tools for biochemical, genetic and physiopathological investigations of mitochondrial diseases. Their immortalization has been previously performed to overcome the limited number of divisions of these primary cells but it has never been systematically evaluate...

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Published in:Neuromuscular disorders : NMD 2007-05, Vol.17 (5), p.368-375
Main Authors: Auré, K, Mamchaoui, K, Frachon, P, Butler-Browne, G.S, Lombès, A, Mouly, V
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - metabolism
Adult
Cell Survival
Cells, Cultured
Child
Child, Preschool
Fibroblasts - drug effects
Fibroblasts - physiology
Glucose - pharmacology
Human fibroblasts
Humans
Immortalization
Middle Aged
Mitochondrial disease
Mitochondrial Myopathies - pathology
Neurology
Oxidative Phosphorylation
Skin - pathology
Telomerase
Telomerase - genetics
Telomerase - metabolism
Time Factors
Transduction, Genetic - methods
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Summary:Abstract Skin fibroblasts are essential tools for biochemical, genetic and physiopathological investigations of mitochondrial diseases. Their immortalization has been previously performed to overcome the limited number of divisions of these primary cells but it has never been systematically evaluated with respect to efficacy and impact on the oxidative phosphorylation (OXPHOS) characteristics of the cells. We successfully immortalized with the human telomerase gene 15 human fibroblasts populations, 4 derived from controls and 11 from patients with diverse respiratory chain defects. Immortalization induced significant but mild modification of the OXPHOS characteristics of the cells with lower rates of oxygen consumption and ATP synthesis associated with their loose coupling. However, it never significantly altered the type and severity of any genetic OXPHOS defect present prior to immortalization. Furthermore, it did not significantly modify the cells’ dependence on glucose and sensitivity to galactose thus showing that immortalized cells could be screened by their nutritional requirement. Immortalized skin fibroblasts with significant OXPHOS defect provide reliable tools for the diagnosis and research of the genetic cause of mitochondrial defects. They also represent precious material to investigate the cellular responses to these defects, even though these should afterwards be verified in unmodified primary cells.
ISSN:0960-8966
1873-2364
DOI:10.1016/j.nmd.2007.01.019