|
|||||
|
|
Restoration of complex V deficiency caused by a novel deletion in the human TMEM70 gene normalizes mitochondrial morphology |
|
| Authors: | Jonckheere An I Huigsloot Merei Lammens Martin Jansen Jitske van den Heuvel Lambert P Spiekerkoetter Ute von Kleist-Retzow Jürgen-Christoph Forkink Marleen Koopman Werner J H Szklarczyk Radek Huynen Martijn A Fransen Jack A Smeitink Jan A M Rodenburg Richard J T |
| Affiliation: | aDepartment of Pediatrics, Nijmegen Center for Mitochondrial Disorders, Laboratory for Genetic, Endocrine, and Metabolic Disorders, Radboud University Nijmegen Medical Center, 6500 HB Nijmegen, The Netherlands;bDepartment of Pathology, Radboud University Nijmegen Medical Center, 6500 HB Nijmegen, The Netherlands;cDepartment of General Pediatrics, University Children's Hospital, Heinrich-Heine-University, 40225 Düsseldorf, Germany;dDepartment of Pediatrics, University of Cologne, 50937 Köln, Germany;eCenter for Molecular Medicine CMMC, University of Cologne, Köln, Germany;fDepartment of Biochemistry (286), Nijmegen Center for Molecular Life Sciences, Radboud University Nijmegen Medical Center, 6525 GA Nijmegen, The Netherlands;gCentre for Molecular and Biomolecular Informatics, Nijmegen Center for Molecular Life Sciences, Radboud University Nijmegen Medical Center, 6525 GA Nijmegen, The Netherlands;hDepartment of Cell Biology, Nijmegen Center for Molecular Life Sciences, Radboud University Nijmegen Medical Center, 6525 GA Nijmegen, The Netherlands |
| Abstract: | We report a fragmented mitochondrial network and swollen and irregularly shaped mitochondria with partial to complete loss of the cristae in fibroblasts of a patient with a novel TMEM70 gene deletion, which could be completely restored by complementation of the TMEM70 genetic defect. Comparative genomics analysis predicted the topology of TMEM70 in the inner mitochondrial membrane, which could be confirmed by immunogold labeling experiments, and showed that the TMEM70 gene is not restricted to higher multi-cellular eukaryotes. This study demonstrates that the role of complex V in mitochondrial cristae morphology applies to human mitochondrial disease pathology. |
| Keywords: | |
| 本文献已被 ScienceDirect PubMed 等数据库收录！ | |