2024-03-28T14:18:10Zhttp://uvadoc.uva.es/oai/requestoai:uvadoc.uva.es:10324/60882021-06-23T09:51:39Zcom_10324_1134com_10324_931com_10324_894col_10324_1213
Altered lipid metabolism in a Drosophila model of Friedreich’s ataxia
Navarro, Juan A.
Ohmann, Elisabeth
Botella, Jose A.
Liebisch, Gerhard
Moltó, Maria D.
Ganfornina Álvarez, María Dolores
Schmitz, Gerd
Schneuwly, Stephan
Sánchez Romero, Diego
Células gliales
Producción Científica
Friedreich’s ataxia (FRDA) is the most common form of autosomal recessive ataxia caused by a deficit in the
mitochondrial protein frataxin. Although demyelination is a common symptom in FRDA patients, no multicellular
model has yet been developed to study the involvement of glial cells in FRDA. Using the recently established
RNAi lines for targeted suppression of frataxin in Drosophila, we were able to study the effects of
general versus glial-specific frataxin downregulation. In particular, we wanted to study the interplay between
lowered frataxin content, lipid accumulation and peroxidation and the consequences of these effects on the
sensitivity to oxidative stress and fly fitness. Interestingly, ubiquitous frataxin reduction leads to an increase
in fatty acids catalyzing an enhancement of lipid peroxidation levels, elevating the intracellular toxic potential.
Specific loss of frataxin in glial cells triggers a similar phenotype which can be visualized by accumulating
lipid droplets in glial cells. This phenotype is associated with a reduced lifespan, an increased sensitivity
to oxidative insult, neurodegenerative effects and a serious impairment of locomotor activity. These symptoms
fit very well with our observation of an increase in intracellular toxicity by lipid peroxides.
Interestingly, co-expression of a Drosophila apolipoprotein D ortholog (glial lazarillo) has a strong protective
effect in our frataxin models, mainly by controlling the level of lipid peroxidation. Our results clearly support
a strong involvement of glial cells and lipid peroxidation in the generation of FRDA-like symptoms.
2014-09-19T11:34:39Z
2015-09-19T23:40:08Z
2010
info:eu-repo/semantics/article
Human Molecular Genetics, 2010, p. 1-13
0964-6906
http://uvadoc.uva.es/handle/10324/6088
10.1093/hmg/ddq183
1
13
Human Molecular Genetics
eng
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
Attribution-NonCommercial-NoDerivatives 4.0 International
Oxford University Press
SI