Post-transcriptional silencing and functional characterization of the Drosophila melanogaster homolog of human Surf1.

TitlePost-transcriptional silencing and functional characterization of the Drosophila melanogaster homolog of human Surf1.
Publication TypeJournal Article
Year of Publication2006
AuthorsZordan, MA, Cisotto, P, Benna, C, Agostino, A, Rizzo, G, Piccin, A, Pegoraro, M, Sandrelli, F, Perini, G, Tognon, G, De Caro, R, Peron, S, Kronniè, TTe, Megighian, A, Reggiani, C, Zeviani, M, Costa, R
Date Published2006 Jan
KeywordsActins, Animals, Drosophila melanogaster, Drosophila Proteins, ELAV Proteins, Electrophysiology, Electroretinography, Female, Gene Expression Regulation, Developmental, Gene Silencing, Genes, Lethal, Humans, Larva, Male, Membrane Proteins, Mice, Mice, Knockout, Mitochondria, Mitochondrial Proteins, Motor Activity, Muscles, Proteins, RNA Interference, RNA Processing, Post-Transcriptional, Trans-Activators

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.

Alternate JournalGenetics
Citation Key10.1534/genetics.105.049072
PubMed ID16172499
PubMed Central IDPMC1456150
Grant ListGP0048Y01 / / Telethon / Italy