First-line Screening of OXPHOS Deficiencies Using Microscale Oxygraphy in Human Skin Fibroblasts: A Preliminary Study

The diagnosis of mitochondrial diseases is a real challenge because of the vast clinical and genetic heterogeneity. Classically, the clinical examination and genetic analysis must be completed by several biochemical assays to confirm the diagnosis of mitochondrial disease. Here, we tested the validi...

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Bibliographic Details
Published in:International journal of medical sciences 2019-01, Vol.16 (7), p.931-938
Main Authors: Germain, Nicolas, Dessein, Anne-Frédérique, Vienne, Jean-Claude, Dobbelaere, Dries, Mention, Karine, Joncquel, Marie, Dekiouk, Salim, Laine, William, Kluza, Jérome, Marchetti, Philippe
Format: Article
Language:English
Subjects:
Adolescent
Biopsy
Cell Culture Techniques
Cell Line
Endocrinology and metabolism
Feasibility Studies
Female
Fibroblasts - cytology
Fibroblasts - pathology
Human health and pathology
Humans
Infant
Infant, Newborn
Life Sciences
Male
Mitochondria - pathology
Mitochondrial Diseases - diagnosis
Mitochondrial Diseases - pathology
Oxidative Phosphorylation
Oxygen - analysis
Oxygen - metabolism
Oxygen Consumption
Pediatrics
Reproducibility of Results
Research Paper
Retrospective Studies
Skin - cytology
Skin - pathology
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Summary:The diagnosis of mitochondrial diseases is a real challenge because of the vast clinical and genetic heterogeneity. Classically, the clinical examination and genetic analysis must be completed by several biochemical assays to confirm the diagnosis of mitochondrial disease. Here, we tested the validity of microscale XF technology in measuring oxygen consumption in human skin fibroblasts isolated from 5 pediatric patients with heterogeneous mitochondrial disorders. We first set up the protocol conditions to allow the determination of respiratory parameters including respiration associated with ATP production, proton leak, maximal respiration, and spare respiratory capacity with reproducibility and repeatability. Maximum respiration and spare capacity were the only parameters decreased in patients irrespective of the type of OXPHOS deficiency. These results were confirmed by high-resolution oxygraphy, the reference method to measure cellular respiration. Given the fact that microscale XF technology allows fast, automated and standardized measurements, we propose to use microscale oxygraphy among the first-line methods to screen OXPHOS deficiencies.
ISSN:1449-1907
1449-1907
DOI:10.7150/ijms.32413