Monday, April 15, 2013

Of flies and men: insights on organismal metabolism from fruit flies

Of flies and men: insights on organismal metabolism from fruit flies. Akhila Rajan and Norbert Perrimon; BMC Biology 2013, 11:38 doi:10.1186/1741-7007-11-38

OPEN ACCESS, FULL TEXT PDF


Altered lipid metabolism in human neurodegenerative disease models

Given the energy needs of neuronal cells, it is not surprising that deficits in energy metabolism manifest themselves most prominently in neuronal cell types. Genes that play a role in lipid homeostasis and mitochondrial function have been linked to adult onset neurodegeneration and have been extensively reviewed elsewhere [4,51,52]. Here we discuss insights obtained from a fly model of Friedreich's ataxia (FRDA) [53]. FRDA is the most common form of an autosomal recessive neurodegenerative disease affecting the central and peripheral nervous systems. It is caused by reduced expression of the mitochondrial protein frataxin, whose deficiency affects citric acid cycle function. Diabetes is a typical symptom of FRDA patients, and electron microscopic analysis of the neurons and cardiac muscles in mouse models shows an increase in lipid droplets [54], suggesting that there may be changes in lipid metabolism. To pursue further the role played by abnormal lipid metabolism in FRDA pathogenesis, Drosophila frataxin was removed from glial cells (neuronal support cells) by RNA interference (RNAi). This resulted in increased lipid droplet accumulation in glial cells and increased sensitivity to oxidative insults, neurodegeneration and impairment in locomotor activity. Interestingly, overexpression of Glial Lazarillo (GLaz) - the Drosophila homolog of human apolipoprotein D, a carrier protein of lipids - confers a protective effect on the Frataxin-RNAi flies. These studies suggest for the first time a specific requirement for frataxin in glial cells, and open the possibility that the control of lipid metabolism by apolipoproteins could represent a new strategy for the treatment of FRDA patients.