Mitochondrial defects and neuromuscular degeneration caused by altered expression of Drosophila Gdap1: implications for the Charcot-Marie-Tooth neuropathy.

TitleMitochondrial defects and neuromuscular degeneration caused by altered expression of Drosophila Gdap1: implications for the Charcot-Marie-Tooth neuropathy.
Publication TypeJournal Article
Year of Publication2015
AuthorsDel Amo, VLopez, Seco-Cervera, M, Garcia-Gimenez, JLuis, Whitworth, AJ, Pallardo, FV, Galindo, MIbo
JournalHum Mol Genet
Volume24
Issue1
Pagination21-36
Date Published2015 Jan 1
ISSN1460-2083
Abstract

One of the genes involved in Charcot-Marie-Tooth (CMT) disease, an inherited peripheral neuropathy, is GDAP1. In this work, we show that there is a true ortholog of this gene in Drosophila, which we have named Gdap1. By up- and down-regulation of Gdap1 in a tissue-specific manner, we show that altering its levels of expression produces changes in mitochondrial size, morphology and distribution, and neuronal and muscular degeneration. Interestingly, muscular degeneration is tissue-autonomous and not dependent on innervation. Metabolic analyses of our experimental genotypes suggest that alterations in oxidative stress are not a primary cause of the neuromuscular degeneration but a long-term consequence of the underlying mitochondrial dysfunction. Our results contribute to a better understanding of the role of mitochondria in CMT disease and pave the way to generate clinically relevant disease models to study the relationship between mitochondrial dynamics and peripheral neurodegeneration.

DOI10.1093/hmg/ddu416
Alternate JournalHum. Mol. Genet.
Citation Key10.1093/hmg/ddu416
PubMed ID25122658