Monday, April 2, 2018

New fly model of mitochondrial disease associated with disruption of SLC25A46

1: Suda K, Ueoka I, Azuma Y, Muraoka Y, Yoshida H, Yamaguchi M. Novel Drosophila model for mitochondrial diseases by targeting of a solute carrier protein SLC25A46. Brain Res. 2018 Mar 28. pii: S0006-8993(18)30163-X. PMID: 29604258.

From the abstract: "Mutations in SLC25A46 gene have been identified in mitochondrial diseases that are sometimes classified as Charcot-Marie-Tooth disease type 2, optic atrophy and Leigh syndrome. Human SLC25A46 functions as a transporter across the outer mitochondrial membrane. However, it is still unknown how the neurodegeneration occurring in these diseases relates to the loss of SLC25A46 function. Drosophila has CG5755 (dSLC25A46) as a single human SLC25A46 homolog. Here we established pan-neuron specific dSLC25A46 knockdown flies, and examined their phenotypes. ... The dSLC25A46 knockdown fly ... recapitulates most of the phenotypes in mitochondrial disease patients, providing a useful tool to study these diseases."

Drosophila analysis helps point to changes in the human gene VPS13D as the cause of a newly identified type of ataxia

Seong E, Insolera R, Dulovic M, Kamsteeg EJ, Trinh J, Brüggemann N, Sandford E, Li S, Ozel AB, Li JZ, Jewett T, Kievit AJA, Münchau A, Shakkottai V, Klein C, Collins C, Lohmann K, van de Warrenburg BP, Burmeister M. Mutations in VPS13D lead to a new recessive ataxia with spasticity and mitochondrial defects. Ann Neurol. 2018 Mar 31. PMID: 29604224.

From the abstract: "... In an international collaboration, we independently performed exome sequencing in seven families with recessive ataxia and/or spastic paraplegia. To evaluate the role of VPS13D mutations, we evaluated a Drosophila knock-out model and investigated mitochondrial function in patient-derived fibroblast cultures. ... Our study demonstrates that compound heterozygous mutations in VPS13D cause movement disorders along the ataxia-spasticity spectrum, making VPS13D the fourth VPS13 paralog involved in neurological disorders. This article is protected by copyright. All rights reserved."