Mitochondrial diseases: Drosophila melanogaster as a model to evaluate potential therapeutics

Foriel, Sarah; Willems, Peter H.G.M.; Smeitink, Jan A.M.; Schenck, Annette; Beyrath, Julien

doi:10.1016/j.biocel.2015.01.024

Cited by 23 publications

(12 citation statements)

References 68 publications

(43 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Frequently used organisms are yeast ( Saccharomyces ) [27], Drosophila [28], Caenorhabditis elegans ( C. elegans ) [29], zebrafish [30], mouse [31], monkey [32], and many more. Drosophila or C. elegans are outstanding models for studying the events of genetic functions related to the common molecular machine.…”

Section: Different Model Organisms and Uniqueness Of Zebrafish Model mentioning

confidence: 99%

Zebrafish: A complete animal model to enumerate the nanoparticle toxicity

et al. 2016

View full text Add to dashboard Cite

Presently, nanotechnology is a multi-trillion dollar business sector that covers a wide range of industries, such as medicine, electronics and chemistry. In the current era, the commercial transition of nanotechnology from research level to industrial level is stimulating the world’s total economic growth. However, commercialization of nanoparticles might offer possible risks once they are liberated in the environment. In recent years, the use of zebrafish (Danio rerio) as an established animal model system for nanoparticle toxicity assay is growing exponentially. In the current in-depth review, we discuss the recent research approaches employing adult zebrafish and their embryos for nanoparticle toxicity assessment. Different types of parameters are being discussed here which are used to evaluate nanoparticle toxicity such as hatching achievement rate, developmental malformation of organs, damage in gill and skin, abnormal behavior (movement impairment), immunotoxicity, genotoxicity or gene expression, neurotoxicity, endocrine system disruption, reproduction toxicity and finally mortality. Furthermore, we have also highlighted the toxic effect of different nanoparticles such as silver nanoparticle, gold nanoparticle, and metal oxide nanoparticles (TiO2, Al2O3, CuO, NiO and ZnO). At the end, future directions of zebrafish model and relevant assays to study nanoparticle toxicity have also been argued.

show abstract

Section: Different Model Organisms and Uniqueness Of Zebrafish Model mentioning

confidence: 99%

Zebrafish: A complete animal model to enumerate the nanoparticle toxicity

et al. 2016

View full text Add to dashboard Cite

show abstract

“…We here report new ubiquitous and tissue-specific knockdown models for mitochondrial CI deficiency, induced by targeted knockdown of the Drosophila NDUFS4 ortholog, dNDUFS4. The relevance of a Drosophila model for mitochondrial disease lies in its capacity to recapitulate the fundamental characteristics of the disease ( Foriel et al, 2015 ; Pandey and Nichols, 2011 ; Sen and Cox, 2017 ). The dNDUFS4 model reported here shows key features of mitochondrial disease with a clear isolated CI deficiency ( Fig.…”

Section: Discussionmentioning

confidence: 99%

“…With the dNDUFS4 KD fly model, we were able to establish a library of phenotypes recapitulating this heterogeneity. These can be further used for therapeutic evaluation ( Foriel et al, 2015 ; Pandey and Nichols, 2011 ). The high level of complexity and severity might, however, impair the development of therapeutic approaches.…”

Section: Discussionmentioning

confidence: 99%

“…Targeting Drosophila OxPhos genes with RNA interference (RNAi) in a spatially and temporally controlled manner has previously contributed to the deciphering of mitochondrial pathophysiology ( Copeland et al, 2009 ; Foriel et al, 2015 ; Sánchez-Martínez et al, 2006 ). Taking advantage of the Drosophila genetic tools available, we inactivated dNDUFS4 ubiquitously and in specific tissues.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Feeding difficulties, a key feature of the Drosophila NDUFS4 mitochondrial disease model

Foriel

Eidhof

Rodenburg

et al. 2018

Disease Models &Amp; Mechanisms

Self Cite

View full text Add to dashboard Cite

Mitochondrial diseases are associated with a wide variety of clinical symptoms and variable degrees of severity. Patients with such diseases generally have a poor prognosis and often an early fatal disease outcome. With an incidence of 1 in 5000 live births and no curative treatments available, relevant animal models to evaluate new therapeutic regimes for mitochondrial diseases are urgently needed. By knocking down ND-18, the unique Drosophila ortholog of NDUFS4, an accessory subunit of the NADH:ubiquinone oxidoreductase (Complex I), we developed and characterized several dNDUFS4 models that recapitulate key features of mitochondrial disease. Like in humans, the dNDUFS4 KD flies display severe feeding difficulties, an aspect of mitochondrial disorders that has so far been largely ignored in animal models. The impact of this finding, and an approach to overcome it, will be discussed in the context of interpreting disease model characterization and intervention studies.This article has an associated First Person interview with the first author of the paper.

show abstract

“…Suitable animal and cellular models are necessary for the understanding of the neuropathology and the development of successful new therapeutic strategies. Different animal and cellular models for mitochondrial neuropathology have been described, concerning isolated OXPHOS defects, mutations in anti-oxidant defense or mitochondrial fusion, defects in mtDNA replication, maintenance or mtRNA processing [11][12][13]. In this paper we used the mitochondrial complex I-deficient Ndufs4 knockout (Ndufs4 −/− ) mouse, which is considered a model for LD [14].…”

Section: Introductionmentioning

confidence: 99%