Originally published as Genetics Published Articles Ahead of Print on September 19, 2005.

Genetics, Vol. 172, 229-241, January 2006, Copyright © 2006
doi:10.1534/genetics.105.049072

Post-transcriptional Silencing and Functional Characterization of the Drosophila melanogaster Homolog of Human Surf1

Mauro A. Zordan^*,1, Paola Cisotto^*,1, Clara Benna^*, Alessandro Agostino, Giorgia Rizzo^*, Alberto Piccin^*, Mirko Pegoraro^*, Federica Sandrelli^*, Giuliana Perini^*, Giuseppe Tognon, Raffaele De Caro, Samantha Peron, Truus te Kronniè^**, Aram Megighian, Carlo Reggiani, Massimo Zeviani and Rodolfo Costa^*,2

^* Department of Biology, Department of Human Anatomy and Physiology and ^** Department of Pediatrics, University of Padova, Italy, Division of Molecular Neurogenetics, National Institute of Neurology "C. Besta," Milano, Italy and CNR Institute of Biomedical Technology, University of Padova, Padova, Italy

² Corresponding author: Department of Biology, University of Padova, Via U. Bassi 58/B, 35131, Padova, Italy.
E-mail: rodolfo.costa{at}unipd.it

Mutations in Surf1, a human gene involved in the assembly of cytochrome c oxidase (COX), cause Leigh syndrome, the most common infantile mitochondrial encephalopathy, characterized by a specific COX deficiency. We report the generation and characterization of functional knockdown (KD) lines for Surf1 in Drosophila. KD was produced by post-transcriptional silencing employing a transgene encoding a dsRNA fragment of the Drosophila homolog of human Surf1, activated by the UAS transcriptional activator. Two alternative drivers, Actin5C–GAL4 or elav–GAL4, were used to induce silencing ubiquitously or in the CNS, respectively. Actin5C–GAL4 KD produced 100% egg-to-adult lethality. Most individuals died as larvae, which were sluggish and small. The few larvae reaching the pupal stage died as early imagos. Electron microscopy of larval muscles showed severely altered mitochondria. elav–GAL4-driven KD individuals developed to adulthood, although cephalic sections revealed low COX-specific activity. Behavioral and electrophysiological abnormalities were detected, including reduced photoresponsiveness in KD larvae using either driver, reduced locomotor speed in Actin5C–GAL4 KD larvae, and impaired optomotor response as well as abnormal electroretinograms in elav–GAL4 KD flies. These results indicate important functions for SURF1 specifically related to COX activity and suggest a crucial role of mitochondrial energy pathways in organogenesis and CNS development and function.

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