Lipid disequilibrium in biological membranes, a possible pathway to neurodegeneration
نویسنده
چکیده
We recently reported that knocking down the enzyme phosphatidylserine decarboxylase, which synthesizes the phospholipid phosphatidylethanolamine (PE) in mitochondria, perturbs the homeostasis of the human Parkinson disease (PD) protein α-synuclein (expressed in yeast or worms). In yeast, low PE in the psd1Δ deletion mutant induces α-synuclein to enter cytoplasmic foci, the level of this protein increases 3-fold compared to wild-type cells, and the mutant cells are severely sick. The metabolite ethanolamine protects both yeast and worms from the deleterious synergistic effects of low mitochondrial PE and α-synuclein. Here we highlight a Drosophila mutant called easily shocked-thought to be a model of epilepsy-that cannot use ethanolamine to synthesize PE. We also highlight recently identified mutated genes associated with defective lipid metabolism in PD and epilepsy patients. We propose that disruptions in lipid homeostasis (synthesis and degradation) may be responsible for some cases of PD and epilepsy.
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