MiPsummer Programme pdf - Mitochondrial Physiology Society

61
Abstract # 31
Generation of a Drosophila model for GRACILE, a mitochondrial complex III disorder
J. Kallijärvi and V. Fellman
Folkhälsan Research Center, Helsinki, Finland and Lund Universitet, Sweden
Background The nuclear BCS1L gene encodes a mitochondrial AAA-family protein that it acts as a
chaperone and incorporates the Rieske iron-sulfur protein into complex III of the respiratory chain 1 .
Different BCS1L mutations cause a wide spectrum of phenotypes in humans, the most severe of
which is a fatal hepatopathy of newborns called
GRACILE syndrome 2 . The GRACILE phenotype
provides an excellent model for CIII deficiency
studies in humans and mice 3 .
Objectives The fruit fly (Drosophila) is an
increasingly important model organism in
mitochondrial and metabolic research. Here, we
have used in vivo RNAi approach to develop a
Drosophila model for GRACILE and for the study
tissue-specific functions of the Bcs1l protein.
Methods RNAi lines were obtained from Vienna
Drosophila RNAi Center and Gal4 driver and
balancer lines either from Bloomington Drosophila
Stock Center or as gifts from other researchers. Fly
maintenance and genetic crosses were performed according to standard protocols.
Results We found that silencing of DmBcs1l in the developing eye caused a mild to severe rough
eye phenotype. Severe eye malfomation was caused by silencing of DmLetm1, which encodes an
essential mitochondrial protein, the mammalian homolog of which is known to interact with
BCS1L.
Conclusions Simple RNAi silencing of Bcs1l in the Drosophila eye yields a non-lethal and easily
scorable phenotype that may prove useful in testing genetic interactions of Bcs1l, and as readout in
dietary and pharmacological experiments.
References
1 Fellman, V. and Kotarsky, H. (2011) Mitochondrial hepatopathies in the newborn period. Seminars
In Fetal & Neonatal Medicine. 16, 222-228
2 Fellman, V., Rapola, J., Pihko, H., Varilo, T. and Raivio, K. O. (1998) Iron-overload disease in
infants involving fetal growth retardation, lactic acidosis, liver haemosiderosis, and aminoaciduria.
Lancet. 351, 490-493
3 Leveen, P., Kotarsky, H., Morgelin, M., Karikoski, R., Elmer, E. and Fellman, V. (2010) The
GRACILE mutation introduced into Bcs1l causes postnatal complex III deficiency: a viable mouse
model for mitochondrial hepatopathy. Hepatology. 53, 437-447