PMID- 16172499
OWN - NLM
STAT- MEDLINE
DCOM- 20060417
LR  - 20220129
IS  - 0016-6731 (Print)
IS  - 0016-6731 (Linking)
VI  - 172
IP  - 1
DP  - 2006 Jan
TI  - Post-transcriptional silencing and functional characterization of the Drosophila 
      melanogaster homolog of human Surf1.
PG  - 229-41
AB  - 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.
FAU - Zordan, Mauro A
AU  - Zordan MA
AD  - CNR Institute of Biomedical Technology, University of Padova, Padova, Italy.
FAU - Cisotto, Paola
AU  - Cisotto P
FAU - Benna, Clara
AU  - Benna C
FAU - Agostino, Alessandro
AU  - Agostino A
FAU - Rizzo, Giorgia
AU  - Rizzo G
FAU - Piccin, Alberto
AU  - Piccin A
FAU - Pegoraro, Mirko
AU  - Pegoraro M
FAU - Sandrelli, Federica
AU  - Sandrelli F
FAU - Perini, Giuliana
AU  - Perini G
FAU - Tognon, Giuseppe
AU  - Tognon G
FAU - De Caro, Raffaele
AU  - De Caro R
FAU - Peron, Samantha
AU  - Peron S
FAU - Kronnie, Truus Te
AU  - Kronnie TT
FAU - Megighian, Aram
AU  - Megighian A
FAU - Reggiani, Carlo
AU  - Reggiani C
FAU - Zeviani, Massimo
AU  - Zeviani M
FAU - Costa, Rodolfo
AU  - Costa R
LA  - eng
GR  - GP0048Y01/TI_/Telethon/Italy
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050919
PL  - United States
TA  - Genetics
JT  - Genetics
JID - 0374636
RN  - 0 (Actins)
RN  - 0 (Drosophila Proteins)
RN  - 0 (ELAV Proteins)
RN  - 0 (ELAV protein, Drosophila)
RN  - 0 (Gal-VP16)
RN  - 0 (Membrane Proteins)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Proteins)
RN  - 0 (Surf-1 protein)
RN  - 0 (Surf1 protein, Drosophila)
RN  - 0 (Trans-Activators)
SB  - IM
MH  - Actins/metabolism
MH  - Animals
MH  - Drosophila Proteins/genetics/metabolism/*physiology
MH  - Drosophila melanogaster/*genetics/growth & development/metabolism
MH  - ELAV Proteins/metabolism
MH  - Electrophysiology
MH  - Electroretinography
MH  - Female
MH  - *Gene Expression Regulation, Developmental
MH  - *Gene Silencing
MH  - Genes, Lethal
MH  - Humans
MH  - Larva/ultrastructure
MH  - Male
MH  - Membrane Proteins
MH  - Mice
MH  - Mice, Knockout
MH  - Mitochondria/metabolism
MH  - Mitochondrial Proteins/genetics/*physiology
MH  - Motor Activity/genetics/*physiology
MH  - Muscles/ultrastructure
MH  - Proteins/genetics/*physiology
MH  - RNA Interference
MH  - *RNA Processing, Post-Transcriptional
MH  - Trans-Activators/genetics/metabolism
PMC - PMC1456150
EDAT- 2005/09/21 09:00
MHDA- 2006/04/18 09:00
PMCR- 2006/04/01
CRDT- 2005/09/21 09:00
PHST- 2005/09/21 09:00 [pubmed]
PHST- 2006/04/18 09:00 [medline]
PHST- 2005/09/21 09:00 [entrez]
PHST- 2006/04/01 00:00 [pmc-release]
AID - genetics.105.049072 [pii]
AID - gen1721229 [pii]
AID - 10.1534/genetics.105.049072 [doi]
PST - ppublish
SO  - Genetics. 2006 Jan;172(1):229-41. doi: 10.1534/genetics.105.049072. Epub 2005 Sep 
      19.