QIL1-dependent assembly of MICOS complex-lethal mutation in C19ORF70 resulting in liver disease and severe neurological retardation

• Verfasst von: Gödiker, J. [VerfasserIn]
• Verfasst von: Langhans, Claus-Dieter [VerfasserIn]
• Titel: QIL1-dependent assembly of MICOS complex-lethal mutation in C19ORF70 resulting in liver disease and severe neurological retardation
• Verf.angabe: J. Gödiker, M. Grüneberg, I. DuChesne, J. Reunert, S. Rust, C. Westermann, Y. Wada, G. Classen, C.D. Langhans, K.P. Schlingmann, R.J. Rodenburg, R. Pohlmann, T. Marquardt
• E-Jahr: 2018
• Jahr: 04 April 2018
• Umfang: 12 S.
• Teil: volume:63
• Teil: year:2018
• Teil: number:6
• Teil: pages:707-716
• Teil: extent:12
• Fussnoten: Gesehen am 08.05.2019
• Titel Quelle: Enthalten in: Journal of human genetics
• Ort Quelle: Basingstoke : Nature Publ. Group, 1977
• Jahr Quelle: 2018
• Band/Heft Quelle: 63(2018), 6, Seite 707-716
• ISSN Quelle: 1435-232X
• DOI: doi:10.1038/s10038-018-0442-y
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1664968059

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.