Int J Med Sci 2019; 16(7):931-938. doi:10.7150/ijms.32413 This issue
1. Univ. Lille, Inserm, UMR-S 1172 - JPArc - Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, F-59000 Lille, France
2. CHU Lille, Centre de Biologie-Pathologie Banque de Tissus, F-59000 Lille, France
3. CHU Lille, Centre de Biologie-Pathologie UF Métabolisme général, hormonal et maladies rares, F-59000 Lille, France
4. CHU Lille, Centre de Référence des maladies héréditaires du métabolisme, F-59000 Lille, France
*JK and PM share co-seniorship of this paper
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.
Keywords: mitochondria, oxidative metabolism, reserve capacity, respiratory chain complex, mitochondrial diseases