Abstract
Seven subunits of the mitochondrial contact site and cristae junction (CJ) organizing system (MICOS) in humans have been recently described in function and structure. QIL1 (also named MIC13) is a small complex that is crucial for the maintenance and assembling of MICOS. A novel mutation of an essential splice site in the C19orf70 gene encoding QIL1 induces severe mitochondrial encephalopathy, hepatopathy and lactate acidosis consistent with psychomotor retardation. In addition, bilateral kidney stones were observed. Disassembly of MICOS complex subunits displays lack of MIC10-MIC26-MIC27-QIL1 subcomplex, resulting in aberrant cristae structure and a loss of cristae junctions and contact sites. In liver and muscle tissue, the activity of the respiratory chain complexes (OXPHOS) was severely impaired. Defects in MICOS complex do not only affect mitochondrial architecture, but also mitochondrial fusion, metabolic signalling, lipid trafficking and cellular electric homeostasis.
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Acknowledgements
We are grateful to the Evangelisches Krankenhaus Bielefeld for providing the MRI scan and sonographic images of the patient. We would like to thank the technicians of the muscle lab and cell culture lab of the Translational Metabolic Laboratory of the RadboudUMC for excellent technical assistance.
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We acknowledge the support by Open Access Publication Fund of University of Muenster.
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Gödiker, J., Grüneberg, M., DuChesne, I. et al. QIL1-dependent assembly of MICOS complex–lethal mutation in C19ORF70 resulting in liver disease and severe neurological retardation. J Hum Genet 63, 707–716 (2018). https://doi.org/10.1038/s10038-018-0442-y
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DOI: https://doi.org/10.1038/s10038-018-0442-y
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