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Title: Mutations in the Intellectual Disability Gene Ube2a Cause Neuronal Dysfunction and Impair Parkin-Dependent Mitophagy
Authors: Haddad, Dominik
Vilain, Sven
Vos, Melissa
Esposito, Giovanni
Matta, Samer
Kalscheuer, Vera M
Craessaerts, Kathleen
Leyssen, Maarten
Nascimento, Rafaella M P
Vianna-Morgante, Angela M
De Strooper, Bart
Van Esch, Hilde
Morais, Vanessa
Verstreken, Patrik # ×
Issue Date: Jun-2013
Publisher: Cell Press
Series Title: Molecular cell vol:50 issue:6 pages:831-43
Article number: S1097-2765(13)00293-1
Abstract: The prevalence of intellectual disability is around 3%; however, the etiology of the disease remains unclear in most cases. We identified a series of patients with X-linked intellectual disability presenting mutations in the Rad6a (Ube2a) gene, which encodes for an E2 ubiquitin-conjugating enzyme. Drosophila deficient for dRad6 display defective synaptic function as a consequence of mitochondrial failure. Similarly, mouse mRad6a (Ube2a) knockout and patient-derived hRad6a (Ube2a) mutant cells show defective mitochondria. Using in vitro and in vivo ubiquitination assays, we show that RAD6A acts as an E2 ubiquitin-conjugating enzyme that, in combination with an E3 ubiquitin ligase such as Parkin, ubiquitinates mitochondrial proteins to facilitate the clearance of dysfunctional mitochondria in cells. Hence, we identify RAD6A as a regulator of Parkin-dependent mitophagy and establish a critical role for RAD6A in maintaining neuronal function.
URI: 
ISSN: 1097-2765
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
Laboratory of Neuronal Communication
Laboratory for the Research of Neurodegenerative Diseases
× corresponding author
# (joint) last author

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