Impairment of Drosophila orthologs of the human orphan protein C19orf12 induces bang sensitivity and neurodegeneration

Arcangela Iuso; Ody C M Sibon; Matteo Gorza; Katharina Heim; Cristina Organisti; Thomas Meitinger; Holger Prokisch

doi:10.1371/journal.pone.0089439

Impairment of Drosophila orthologs of the human orphan protein C19orf12 induces bang sensitivity and neurodegeneration

PLoS One. 2014 Feb 21;9(2):e89439. doi: 10.1371/journal.pone.0089439. eCollection 2014.

Authors

Arcangela Iuso¹, Ody C M Sibon², Matteo Gorza³, Katharina Heim¹, Cristina Organisti⁴, Thomas Meitinger¹, Holger Prokisch¹

Affiliations

¹ Institute of Human Genetics, Technische Universität München, Munich, Germany ; Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany.
² Department of Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
³ Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany.
⁴ Sensory Neurogenetics Research Group, Max Planck Institute of Neurobiology, Martinsried, Germany.

Abstract

Mutations in the orphan gene C19orf12 were identified as a genetic cause in a subgroup of patients with NBIA, a neurodegenerative disorder characterized by deposits of iron in the basal ganglia. C19orf12 was shown to be localized in mitochondria, however, nothing is known about its activity and no functional link exists to the clinical phenotype of the patients. This situation led us to investigate the effects of C19orf12 down-regulation in the model organism Drosophila melanogaster. Two genes are present in D. melanogaster, which are orthologs of C19orf12, CG3740 and CG11671. Here we provide evidence that transgenic flies with impaired C19orf12 homologs reflect the neurodegenerative phenotype and represent a valid tool to further analyze the pathomechanism in C19orf12-associated NBIA.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Animals, Genetically Modified
Behavior, Animal / physiology
Brain / metabolism*
Down-Regulation
Drosophila Proteins / genetics*
Drosophila Proteins / metabolism
Drosophila melanogaster
Mitochondrial Proteins / genetics*
Mitochondrial Proteins / metabolism
Nerve Degeneration / genetics*
Nerve Degeneration / metabolism
Neurons / metabolism*
Stress, Physiological / genetics

Substances

C19orf12 protein, human
Drosophila Proteins
Mitochondrial Proteins

Grants and funding

This work was funded by the NBIA Disorders Association Grant 2011 (AI), by the VICI grant from the Dutch organization of Scientific Research, NOW (OS), and by the European Commission’s Seventh Framework Program (FP7/2007–2013, HEALTH-F2-2011, grant agreement No. 277984, TIRCON) (OS, HP, TM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.