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Leigh Syndrome in Drosophila melanogaster: morphological and biochemical characterization of Surf1 post-transcriptional silencing.

ABSTRACT: Leigh Syndrome (LS) is the most common early-onset, progressive mitochondrial encephalopathy usually leading to early death. The single most prevalent cause of LS is occurrence of mutations in the hSurf1 gene. LSSurf1 patients show a marked and specific decrease in the activity of mitochondrial respiratory chain complex IV (cytochrome c oxidase, COX). hSurf1 encodes an inner membrane mitochondrial protein involved in COX assembly. We established a D. melanogaster model of LS based on the post-transcriptional silencing of CG9943, the Drosophila homolog of hSurf1. Knock down of Surf1 was induced (i) ubiquitously, which led to larval lethality; (ii) in the mesodermal derivatives, which led to pupal lethality; (iii) in the central nervous system, which allowed survival; and (iv) at specific developmental stages. A biochemical characterization was carried out in knock down individuals, which unexpectedly revealed defects in all complexes of the mitochondrial respiratory chain (MRC) included the F-ATP synthase (complex V) in larvae, and a COX-specific impairment in adults. Silencing of Surf1 expression in Drosophila S2R+ cells led to loss of COX activity associated with decreased oxygen consumption. We conclude that Surf1 is essential for COX activity and mitochondrial function in D. melanogaster, and provide a new tool to clarify the pathogenic mechanisms of LS.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE58301 | GEO | 2014/11/04

SECONDARY ACCESSION(S): PRJNA251958

REPOSITORIES: GEO

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Defective metabolic programming impairs early neuronal morphogenesis in neural cultures and an organoid model of Leigh syndrome [rRNA-depleted organoids]

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2009-02-20 | E-MEXP-585 | biostudies-arrayexpress

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