RT info:eu-repo/semantics/article
T1 Altered lipid metabolism in a Drosophila model of Friedreich’s ataxia
A1 Navarro, Juan A.
A1 Ohmann, Elisabeth
A1 Sánchez Romero, Diego
A1 Botella, Jose A.
A1 Liebisch, Gerhard
A1 Moltó, Maria D.
A1 Ganfornina Álvarez, María Dolores
A1 Schmitz, Gerd
A1 Schneuwly, Stephan
K1 Células gliales
AB Friedreich’s ataxia (FRDA) is the most common form of autosomal recessive ataxia caused by a deficit in themitochondrial protein frataxin. Although demyelination is a common symptom in FRDA patients, no multicellularmodel has yet been developed to study the involvement of glial cells in FRDA. Using the recently establishedRNAi lines for targeted suppression of frataxin in Drosophila, we were able to study the effects ofgeneral versus glial-specific frataxin downregulation. In particular, we wanted to study the interplay betweenlowered frataxin content, lipid accumulation and peroxidation and the consequences of these effects on thesensitivity to oxidative stress and fly fitness. Interestingly, ubiquitous frataxin reduction leads to an increasein 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 accumulatinglipid droplets in glial cells. This phenotype is associated with a reduced lifespan, an increased sensitivityto oxidative insult, neurodegenerative effects and a serious impairment of locomotor activity. These symptomsfit 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 protectiveeffect in our frataxin models, mainly by controlling the level of lipid peroxidation. Our results clearly supporta strong involvement of glial cells and lipid peroxidation in the generation of FRDA-like symptoms.
PB Oxford University Press
SN 0964-6906
YR 2010
FD 2010
LK http://uvadoc.uva.es/handle/10324/6088
UL http://uvadoc.uva.es/handle/10324/6088
LA eng
NO Human Molecular Genetics, 2010, p. 1-13
NO Producción Científica
DS UVaDOC
RD 25-abr-2024