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Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/12729

Title: Caenorhabditis elegans, a pluricellular model organism to screen new genes involvedin mitochondrial genome maintenance
Authors: Addo, Matthew Glover
Cossard, Raynald
Pichard, Damien
Obiri-Danso, Kwasi
Rötig, Agnès
et. al
Keywords: Mitochondria
mtDNA maintenance
Nematode/Caenorhabditis elegans
Issue Date: 24-May-2010
Publisher: Elsevier B.V
Citation: Biochimica et Biophysica Acta 1802 (2010) 765–773. doi:10.1016/j.bbadis.2010.05.007
Abstract: The inheritance of functional mitochondria depends on faithful replication and transmission ofmitochondrial DNA (mtDNA). A large and heterogeneous group of human disorders is associated withmitochondrial genome quantitative and qualitative anomalies. Several nuclear genes have been shown toaccount for these severe OXPHOS disorders. However, in several cases, the disease-causing mutations stillremain unknown.Caenorhabditis eleganshas been largely used for studying various biological functions because thismulticellular organism has short life cycle and is easy to grow in the laboratory. Mitochondrial functionsare relatively well conserved between human andC. elegans, and heteroplasmy exists in this organism as inhuman.C. eleganstherefore represents a useful tool for studying mtDNA maintenance. Suppression by RNAinterference of genes involved in mtDNA replication such aspolg-1, encoding the mitochondrial DNApolymerase, results in reduced mtDNA copy number but in a normal phenotype of the F1 worms. Bycombining RNAi of genes involved in mtDNA maintenance and EtBr exposure, we were able to reveal astrong and specific phenotype (developmental larval arrest) associated to a severe decrease of mtDNA copynumber. Moreover, we tested and validated the screen efficiency for human orthologous genes encodingmitochondrial nucleoid proteins. This allowed us to identify several genes that seem to be closely related tomtDNA maintenance inC. elegans.This work reports afirst step in the further development of a large-scale screening inC. elegansthat shouldallow to identify new genes of mtDNA maintenance whose human orthologs will obviously constitute newcandidate genes for patients with quantitative or qualitative mtDNA anomalies.
Description: An article published by Elsevier B.V. and also available at doi:10.1016/j.bbadis.2010.05.007
URI: http://hdl.handle.net/123456789/12729
Appears in Collections:College of Science

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