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Corrigendum Free access | 10.1172/JCI76634

A spastic paraplegia mouse model reveals REEP1-dependent ER shaping

Christian Beetz,1 Nicole Koch,2 Mukhran Khundadze,3 Geraldine Zimmer,3 Sandor Nietzsche,4 Nicole Hertel,5 Antje-Kathrin Huebner,3 Rizwan Mumtaz,3 Michaela Schweizer,6 Elisabeth Dirren,7 Kathrin N. Karle,8,9 Andrey Irintchev,9 Victoria Alvarez,10 Christoph Redies,5 Martin Westermann,4 Ingo Kurth,3 Thomas Deufel,1 Michael M. Kessels,2 Britta Qualmann,2 and Christian A. Hübner3

1Institute of Clinical Chemistry and Laboratory Diagnostics, 2Institute of Biochemistry I, 3Institute of Human Genetics, 4Electron Microscopy Center, and 5Institute of Anatomy I, University Hospital Jena, Friedrich-Schiller-University Jena, Jena, Germany. 6Zentrum für Molekulare Neurobiologie Hamburg (ZMNH), University Hamburg, Hamburg, Germany. 7Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, EPFL, Lausanne, Switzerland. 8Department of Neurology and Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. 9Deutsche Zentrum für Neurodegenerative Erkrankungen (DZNE), Tübingen, Germany. 10Department of Otorhinolaryngology, Jena University Hospital, Friedrich-Schiller-University Jena, Jena, Germany. 11Laboratory of Molecular Genetics — Genetic Unit, Hospital Universitario Central de Asturias, Oviedo, Spain.

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1Institute of Clinical Chemistry and Laboratory Diagnostics, 2Institute of Biochemistry I, 3Institute of Human Genetics, 4Electron Microscopy Center, and 5Institute of Anatomy I, University Hospital Jena, Friedrich-Schiller-University Jena, Jena, Germany. 6Zentrum für Molekulare Neurobiologie Hamburg (ZMNH), University Hamburg, Hamburg, Germany. 7Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, EPFL, Lausanne, Switzerland. 8Department of Neurology and Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. 9Deutsche Zentrum für Neurodegenerative Erkrankungen (DZNE), Tübingen, Germany. 10Department of Otorhinolaryngology, Jena University Hospital, Friedrich-Schiller-University Jena, Jena, Germany. 11Laboratory of Molecular Genetics — Genetic Unit, Hospital Universitario Central de Asturias, Oviedo, Spain.

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1Institute of Clinical Chemistry and Laboratory Diagnostics, 2Institute of Biochemistry I, 3Institute of Human Genetics, 4Electron Microscopy Center, and 5Institute of Anatomy I, University Hospital Jena, Friedrich-Schiller-University Jena, Jena, Germany. 6Zentrum für Molekulare Neurobiologie Hamburg (ZMNH), University Hamburg, Hamburg, Germany. 7Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, EPFL, Lausanne, Switzerland. 8Department of Neurology and Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. 9Deutsche Zentrum für Neurodegenerative Erkrankungen (DZNE), Tübingen, Germany. 10Department of Otorhinolaryngology, Jena University Hospital, Friedrich-Schiller-University Jena, Jena, Germany. 11Laboratory of Molecular Genetics — Genetic Unit, Hospital Universitario Central de Asturias, Oviedo, Spain.

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1Institute of Clinical Chemistry and Laboratory Diagnostics, 2Institute of Biochemistry I, 3Institute of Human Genetics, 4Electron Microscopy Center, and 5Institute of Anatomy I, University Hospital Jena, Friedrich-Schiller-University Jena, Jena, Germany. 6Zentrum für Molekulare Neurobiologie Hamburg (ZMNH), University Hamburg, Hamburg, Germany. 7Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, EPFL, Lausanne, Switzerland. 8Department of Neurology and Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. 9Deutsche Zentrum für Neurodegenerative Erkrankungen (DZNE), Tübingen, Germany. 10Department of Otorhinolaryngology, Jena University Hospital, Friedrich-Schiller-University Jena, Jena, Germany. 11Laboratory of Molecular Genetics — Genetic Unit, Hospital Universitario Central de Asturias, Oviedo, Spain.

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1Institute of Clinical Chemistry and Laboratory Diagnostics, 2Institute of Biochemistry I, 3Institute of Human Genetics, 4Electron Microscopy Center, and 5Institute of Anatomy I, University Hospital Jena, Friedrich-Schiller-University Jena, Jena, Germany. 6Zentrum für Molekulare Neurobiologie Hamburg (ZMNH), University Hamburg, Hamburg, Germany. 7Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, EPFL, Lausanne, Switzerland. 8Department of Neurology and Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. 9Deutsche Zentrum für Neurodegenerative Erkrankungen (DZNE), Tübingen, Germany. 10Department of Otorhinolaryngology, Jena University Hospital, Friedrich-Schiller-University Jena, Jena, Germany. 11Laboratory of Molecular Genetics — Genetic Unit, Hospital Universitario Central de Asturias, Oviedo, Spain.

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1Institute of Clinical Chemistry and Laboratory Diagnostics, 2Institute of Biochemistry I, 3Institute of Human Genetics, 4Electron Microscopy Center, and 5Institute of Anatomy I, University Hospital Jena, Friedrich-Schiller-University Jena, Jena, Germany. 6Zentrum für Molekulare Neurobiologie Hamburg (ZMNH), University Hamburg, Hamburg, Germany. 7Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, EPFL, Lausanne, Switzerland. 8Department of Neurology and Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. 9Deutsche Zentrum für Neurodegenerative Erkrankungen (DZNE), Tübingen, Germany. 10Department of Otorhinolaryngology, Jena University Hospital, Friedrich-Schiller-University Jena, Jena, Germany. 11Laboratory of Molecular Genetics — Genetic Unit, Hospital Universitario Central de Asturias, Oviedo, Spain.

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1Institute of Clinical Chemistry and Laboratory Diagnostics, 2Institute of Biochemistry I, 3Institute of Human Genetics, 4Electron Microscopy Center, and 5Institute of Anatomy I, University Hospital Jena, Friedrich-Schiller-University Jena, Jena, Germany. 6Zentrum für Molekulare Neurobiologie Hamburg (ZMNH), University Hamburg, Hamburg, Germany. 7Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, EPFL, Lausanne, Switzerland. 8Department of Neurology and Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. 9Deutsche Zentrum für Neurodegenerative Erkrankungen (DZNE), Tübingen, Germany. 10Department of Otorhinolaryngology, Jena University Hospital, Friedrich-Schiller-University Jena, Jena, Germany. 11Laboratory of Molecular Genetics — Genetic Unit, Hospital Universitario Central de Asturias, Oviedo, Spain.

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1Institute of Clinical Chemistry and Laboratory Diagnostics, 2Institute of Biochemistry I, 3Institute of Human Genetics, 4Electron Microscopy Center, and 5Institute of Anatomy I, University Hospital Jena, Friedrich-Schiller-University Jena, Jena, Germany. 6Zentrum für Molekulare Neurobiologie Hamburg (ZMNH), University Hamburg, Hamburg, Germany. 7Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, EPFL, Lausanne, Switzerland. 8Department of Neurology and Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. 9Deutsche Zentrum für Neurodegenerative Erkrankungen (DZNE), Tübingen, Germany. 10Department of Otorhinolaryngology, Jena University Hospital, Friedrich-Schiller-University Jena, Jena, Germany. 11Laboratory of Molecular Genetics — Genetic Unit, Hospital Universitario Central de Asturias, Oviedo, Spain.

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1Institute of Clinical Chemistry and Laboratory Diagnostics, 2Institute of Biochemistry I, 3Institute of Human Genetics, 4Electron Microscopy Center, and 5Institute of Anatomy I, University Hospital Jena, Friedrich-Schiller-University Jena, Jena, Germany. 6Zentrum für Molekulare Neurobiologie Hamburg (ZMNH), University Hamburg, Hamburg, Germany. 7Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, EPFL, Lausanne, Switzerland. 8Department of Neurology and Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. 9Deutsche Zentrum für Neurodegenerative Erkrankungen (DZNE), Tübingen, Germany. 10Department of Otorhinolaryngology, Jena University Hospital, Friedrich-Schiller-University Jena, Jena, Germany. 11Laboratory of Molecular Genetics — Genetic Unit, Hospital Universitario Central de Asturias, Oviedo, Spain.

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1Institute of Clinical Chemistry and Laboratory Diagnostics, 2Institute of Biochemistry I, 3Institute of Human Genetics, 4Electron Microscopy Center, and 5Institute of Anatomy I, University Hospital Jena, Friedrich-Schiller-University Jena, Jena, Germany. 6Zentrum für Molekulare Neurobiologie Hamburg (ZMNH), University Hamburg, Hamburg, Germany. 7Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, EPFL, Lausanne, Switzerland. 8Department of Neurology and Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. 9Deutsche Zentrum für Neurodegenerative Erkrankungen (DZNE), Tübingen, Germany. 10Department of Otorhinolaryngology, Jena University Hospital, Friedrich-Schiller-University Jena, Jena, Germany. 11Laboratory of Molecular Genetics — Genetic Unit, Hospital Universitario Central de Asturias, Oviedo, Spain.

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1Institute of Clinical Chemistry and Laboratory Diagnostics, 2Institute of Biochemistry I, 3Institute of Human Genetics, 4Electron Microscopy Center, and 5Institute of Anatomy I, University Hospital Jena, Friedrich-Schiller-University Jena, Jena, Germany. 6Zentrum für Molekulare Neurobiologie Hamburg (ZMNH), University Hamburg, Hamburg, Germany. 7Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, EPFL, Lausanne, Switzerland. 8Department of Neurology and Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. 9Deutsche Zentrum für Neurodegenerative Erkrankungen (DZNE), Tübingen, Germany. 10Department of Otorhinolaryngology, Jena University Hospital, Friedrich-Schiller-University Jena, Jena, Germany. 11Laboratory of Molecular Genetics — Genetic Unit, Hospital Universitario Central de Asturias, Oviedo, Spain.

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1Institute of Clinical Chemistry and Laboratory Diagnostics, 2Institute of Biochemistry I, 3Institute of Human Genetics, 4Electron Microscopy Center, and 5Institute of Anatomy I, University Hospital Jena, Friedrich-Schiller-University Jena, Jena, Germany. 6Zentrum für Molekulare Neurobiologie Hamburg (ZMNH), University Hamburg, Hamburg, Germany. 7Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, EPFL, Lausanne, Switzerland. 8Department of Neurology and Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. 9Deutsche Zentrum für Neurodegenerative Erkrankungen (DZNE), Tübingen, Germany. 10Department of Otorhinolaryngology, Jena University Hospital, Friedrich-Schiller-University Jena, Jena, Germany. 11Laboratory of Molecular Genetics — Genetic Unit, Hospital Universitario Central de Asturias, Oviedo, Spain.

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1Institute of Clinical Chemistry and Laboratory Diagnostics, 2Institute of Biochemistry I, 3Institute of Human Genetics, 4Electron Microscopy Center, and 5Institute of Anatomy I, University Hospital Jena, Friedrich-Schiller-University Jena, Jena, Germany. 6Zentrum für Molekulare Neurobiologie Hamburg (ZMNH), University Hamburg, Hamburg, Germany. 7Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, EPFL, Lausanne, Switzerland. 8Department of Neurology and Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. 9Deutsche Zentrum für Neurodegenerative Erkrankungen (DZNE), Tübingen, Germany. 10Department of Otorhinolaryngology, Jena University Hospital, Friedrich-Schiller-University Jena, Jena, Germany. 11Laboratory of Molecular Genetics — Genetic Unit, Hospital Universitario Central de Asturias, Oviedo, Spain.

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1Institute of Clinical Chemistry and Laboratory Diagnostics, 2Institute of Biochemistry I, 3Institute of Human Genetics, 4Electron Microscopy Center, and 5Institute of Anatomy I, University Hospital Jena, Friedrich-Schiller-University Jena, Jena, Germany. 6Zentrum für Molekulare Neurobiologie Hamburg (ZMNH), University Hamburg, Hamburg, Germany. 7Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, EPFL, Lausanne, Switzerland. 8Department of Neurology and Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. 9Deutsche Zentrum für Neurodegenerative Erkrankungen (DZNE), Tübingen, Germany. 10Department of Otorhinolaryngology, Jena University Hospital, Friedrich-Schiller-University Jena, Jena, Germany. 11Laboratory of Molecular Genetics — Genetic Unit, Hospital Universitario Central de Asturias, Oviedo, Spain.

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1Institute of Clinical Chemistry and Laboratory Diagnostics, 2Institute of Biochemistry I, 3Institute of Human Genetics, 4Electron Microscopy Center, and 5Institute of Anatomy I, University Hospital Jena, Friedrich-Schiller-University Jena, Jena, Germany. 6Zentrum für Molekulare Neurobiologie Hamburg (ZMNH), University Hamburg, Hamburg, Germany. 7Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, EPFL, Lausanne, Switzerland. 8Department of Neurology and Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. 9Deutsche Zentrum für Neurodegenerative Erkrankungen (DZNE), Tübingen, Germany. 10Department of Otorhinolaryngology, Jena University Hospital, Friedrich-Schiller-University Jena, Jena, Germany. 11Laboratory of Molecular Genetics — Genetic Unit, Hospital Universitario Central de Asturias, Oviedo, Spain.

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1Institute of Clinical Chemistry and Laboratory Diagnostics, 2Institute of Biochemistry I, 3Institute of Human Genetics, 4Electron Microscopy Center, and 5Institute of Anatomy I, University Hospital Jena, Friedrich-Schiller-University Jena, Jena, Germany. 6Zentrum für Molekulare Neurobiologie Hamburg (ZMNH), University Hamburg, Hamburg, Germany. 7Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, EPFL, Lausanne, Switzerland. 8Department of Neurology and Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. 9Deutsche Zentrum für Neurodegenerative Erkrankungen (DZNE), Tübingen, Germany. 10Department of Otorhinolaryngology, Jena University Hospital, Friedrich-Schiller-University Jena, Jena, Germany. 11Laboratory of Molecular Genetics — Genetic Unit, Hospital Universitario Central de Asturias, Oviedo, Spain.

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1Institute of Clinical Chemistry and Laboratory Diagnostics, 2Institute of Biochemistry I, 3Institute of Human Genetics, 4Electron Microscopy Center, and 5Institute of Anatomy I, University Hospital Jena, Friedrich-Schiller-University Jena, Jena, Germany. 6Zentrum für Molekulare Neurobiologie Hamburg (ZMNH), University Hamburg, Hamburg, Germany. 7Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, EPFL, Lausanne, Switzerland. 8Department of Neurology and Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. 9Deutsche Zentrum für Neurodegenerative Erkrankungen (DZNE), Tübingen, Germany. 10Department of Otorhinolaryngology, Jena University Hospital, Friedrich-Schiller-University Jena, Jena, Germany. 11Laboratory of Molecular Genetics — Genetic Unit, Hospital Universitario Central de Asturias, Oviedo, Spain.

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1Institute of Clinical Chemistry and Laboratory Diagnostics, 2Institute of Biochemistry I, 3Institute of Human Genetics, 4Electron Microscopy Center, and 5Institute of Anatomy I, University Hospital Jena, Friedrich-Schiller-University Jena, Jena, Germany. 6Zentrum für Molekulare Neurobiologie Hamburg (ZMNH), University Hamburg, Hamburg, Germany. 7Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, EPFL, Lausanne, Switzerland. 8Department of Neurology and Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. 9Deutsche Zentrum für Neurodegenerative Erkrankungen (DZNE), Tübingen, Germany. 10Department of Otorhinolaryngology, Jena University Hospital, Friedrich-Schiller-University Jena, Jena, Germany. 11Laboratory of Molecular Genetics — Genetic Unit, Hospital Universitario Central de Asturias, Oviedo, Spain.

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1Institute of Clinical Chemistry and Laboratory Diagnostics, 2Institute of Biochemistry I, 3Institute of Human Genetics, 4Electron Microscopy Center, and 5Institute of Anatomy I, University Hospital Jena, Friedrich-Schiller-University Jena, Jena, Germany. 6Zentrum für Molekulare Neurobiologie Hamburg (ZMNH), University Hamburg, Hamburg, Germany. 7Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, EPFL, Lausanne, Switzerland. 8Department of Neurology and Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. 9Deutsche Zentrum für Neurodegenerative Erkrankungen (DZNE), Tübingen, Germany. 10Department of Otorhinolaryngology, Jena University Hospital, Friedrich-Schiller-University Jena, Jena, Germany. 11Laboratory of Molecular Genetics — Genetic Unit, Hospital Universitario Central de Asturias, Oviedo, Spain.

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1Institute of Clinical Chemistry and Laboratory Diagnostics, 2Institute of Biochemistry I, 3Institute of Human Genetics, 4Electron Microscopy Center, and 5Institute of Anatomy I, University Hospital Jena, Friedrich-Schiller-University Jena, Jena, Germany. 6Zentrum für Molekulare Neurobiologie Hamburg (ZMNH), University Hamburg, Hamburg, Germany. 7Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, EPFL, Lausanne, Switzerland. 8Department of Neurology and Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. 9Deutsche Zentrum für Neurodegenerative Erkrankungen (DZNE), Tübingen, Germany. 10Department of Otorhinolaryngology, Jena University Hospital, Friedrich-Schiller-University Jena, Jena, Germany. 11Laboratory of Molecular Genetics — Genetic Unit, Hospital Universitario Central de Asturias, Oviedo, Spain.

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First published June 2, 2014 - More info

Published in Volume 124, Issue 6 on June 2, 2014
J Clin Invest. 2014;124(6):2809–2809. https://doi.org/10.1172/JCI76634.
© 2014 The American Society for Clinical Investigation
First published June 2, 2014 - Version history

Related article:

A spastic paraplegia mouse model reveals REEP1-dependent ER shaping
Christian Beetz, … , Britta Qualmann, Christian A. Hübner
Christian Beetz, … , Britta Qualmann, Christian A. Hübner
Research Article

A spastic paraplegia mouse model reveals REEP1-dependent ER shaping

Abstract

Axonopathies are a group of clinically diverse disorders characterized by the progressive degeneration of the axons of specific neurons. In hereditary spastic paraplegia (HSP), the axons of cortical motor neurons degenerate and cause a spastic movement disorder. HSP is linked to mutations in several loci known collectively as the spastic paraplegia genes (SPGs). We identified a heterozygous receptor accessory protein 1 (REEP1) exon 2 deletion in a patient suffering from the autosomal dominantly inherited HSP variant SPG31. We generated the corresponding mouse model to study the underlying cellular pathology. Mice with heterozygous deletion of exon 2 in Reep1 displayed a gait disorder closely resembling SPG31 in humans. Homozygous exon 2 deletion resulted in the complete loss of REEP1 and a more severe phenotype with earlier onset. At the molecular level, we demonstrated that REEP1 is a neuron-specific, membrane-binding, and membrane curvature–inducing protein that resides in the ER. We further show that Reep1 expression was prominent in cortical motor neurons. In REEP1-deficient mice, these neurons showed reduced complexity of the peripheral ER upon ultrastructural analysis. Our study connects proper neuronal ER architecture to long-term axon survival.

Authors

Christian Beetz, Nicole Koch, Mukhran Khundadze, Geraldine Zimmer, Sandor Nietzsche, Nicole Hertel, Antje-Kathrin Huebner, Rizwan Mumtaz, Michaela Schweizer, Elisabeth Dirren, Kathrin N. Karle, Andrey Irintchev, Victoria Alvarez, Christoph Redies, Martin Westermann, Ingo Kurth, Thomas Deufel, Michael M. Kessels, Britta Qualmann, Christian A. Hübner

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Original citation: J. Clin. Invest. 2014;123(10):4273–4282. doi:10.1172/JCI65665.

Citation for this corrigendum: J. Clin. Invest. 2014;124(6):2809. doi:10.1172/JCI76634.

During the preparation of this manuscript, one of Kathrin N. Karle’s affiliations was inadvertently omitted. The correct affiliation list is above. In addition, information was omitted from the Acknowledgments section. The correct Acknowledgments section is below.

We thank M. Öhler, B. Schade, K. Schorr, A. Büschel, K. Stein, and R. Kaiser for their excellent technical assistance. We thank Nadine Breitkreutz for excellent technical analyses. We thank C. Kaether for valuable discussions and Laura McMillan for editing the final manuscript. This work was supported by grants from the Deutsche Forschungsgemeinschaft (DFG) to M.M. Kessels (KE685/3-1), B. Qualmann (QU116/6-1), C. Beetz (BE4069/1-1), T. Deufel and C.A. Hübner (DE307/8-1), and C.A. Hübner (HU800/6-1). The work of Kathrin N. Karle was supported by the German Ministry of Education and Research (BMBF) through funding to the mitoNET (01GM1113E).

The authors regret the error.

Version history
  • Version 1 (June 2, 2014): No description
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