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Updated: Mar 22, 2026

Hybrid Clear/Blue Native Electrophoresis for the Separation and Analysis of Mitochondrial Respiratory Chain Supercomplexes
Published on: May 19, 2019
Respiratory chain deficiency in nonmitochondrial disease
Angela Pyle1, Helen J Nightingale1, Helen Griffin1
1Wellcome Trust Centre for Mitochondrial Research (A.P., H.J.N., H.G., K.D., M.S.-K., P.F.C., R.H.), Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom; Medical Genetics Center (A.A., L.F., B.C., S.K., E.H.-F.), Munich, Germany; Division of Neuropediatrics and Muscle Disorders (J.K.), University Medical Center, Freiburg, Germany; Department of Paediatrics (I.B., M.C.), University Hospital Center Zagreb & University of Zagreb, School of Medicine, Zagreb, Croatia; Department of Paediatrics (M.K.), Hospital Baden-Baden, Germany; and Department of Molecular Genetics and Diagnostics (V.K.), NIEH, Budapest, Hungary.
Objective:
In this study, we report 5 patients with heterogeneous phenotypes and biochemical evidence of respiratory chain (RC) deficiency; however, the molecular diagnosis is not mitochondrial disease.
Methods:
The reported patients were identified from a cohort of 60 patients in whom RC enzyme deficiency suggested mitochondrial disease and underwent whole-exome sequencing.
Results:
Five patients had disease-causing variants in nonmitochondrial disease genes ORAI1, CAPN3, COLQ, EXOSC8, and ANO10, which would have been missed on targeted next-generation panels or on MitoExome analysis.
Conclusions:
Our data demonstrate that RC abnormalities may be secondary to various cellular processes, including calcium metabolism, neuromuscular transmission, and abnormal messenger RNA degradation.
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