Proceedings of the National Academy of Sciences · 2006 · 42 citations · 32 references
Life SciencesGeneticsMolecular BiologyAgingMitochondrial BiologyMitochondrial GeneticsEnergy MetabolismGenetics Of AgingLipid HomeostasisLipid MetabolismLongevityMitochondrial MetabolismCellular Oxidative Stress ResponseDrosophila ModelsEnergy Metabolism DefectsEnergy Metabolism RegulationFatty AcidsLipid Metabolism PathwaysOxidative Stress Response GeneticsOxidative Stress Response Pathways
Deregulation of energy metabolism by external interventions or mutations in metabolic genes can extend lifespan in a wide range of species. We describe mutations in Drosophila melanogaster that confer resistance to oxidative stress and display a longevity phenotype. These phenotypes are associated with molecular lesions in a hitherto uncharacterized gene we named Enigma. We show that Enigma encodes a mitochondrial protein with homology to enzymes of the beta-oxidation of fatty acids and that mutations in this locus affect lipid homeostasis. Our analysis provides further support to the notion that lipid metabolism may play a central role in metazoan lifespan regulation.
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