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

Caterina Da-Rè, Sophia Von Stockum, Alberto Biscontin, Caterina Millino, Paola Cisotto, Mauro A. Zordan, Massimo Zeviani, Paolo Bernardi, Cristiano De Pittà, Rodolfo Costa

Research output: Contribution to journalArticle

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 SURF1 gene, and LSSurf1 patients show a ubiquitous and specific decrease in the activity of mitochondrial respiratory chain complex IV (cytochrome c oxidase, COX). SURF1 encodes an inner membrane mitochondrial protein involved in COX assembly. We established a Drosophila melanogaster model of LS based on the post-transcriptional silencing of CG9943, the Drosophila homolog of SURF1. Knockdown of Surf1 was induced ubiquitously in larvae and adults, which led to lethality; in the mesodermal derivatives, which led to pupal lethality; or in the central nervous system, which allowed survival. A biochemical characterization was carried out in knockdown individuals, which revealed that larvae unexpectedly displayed defects in all complexes of the mitochondrial respiratory chain and in the F-ATP synthase, while adults had a COX-selective impairment. Silencing of Surf1 expression in Drosophila S2R+ cells led to selective loss of COX activity associated with decreased oxygen consumption and respiratory reserve. We conclude that Surf1 is essential for COX activity and mitochondrial function in D. melanogaster, thus providing a new tool that may help clarify the pathogenic mechanisms of LS.

Original languageEnglish
Pages (from-to)29235-29246
Number of pages12
JournalJournal of Biological Chemistry
Volume289
Issue number42
DOIs
Publication statusPublished - Oct 17 2014

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

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