PMID:19804760

Citation	Zid, BM, Rogers, AN, Katewa, SD, Vargas, MA, Kolipinski, MC, Lu, TA, Benzer, S and Kapahi, P (2009) 4E-BP extends lifespan upon dietary restriction by enhancing mitochondrial activity in Drosophila. Cell 139:149-60
Abstract	Dietary restriction (DR) extends lifespan in multiple species. To examine the mechanisms of lifespan extension upon DR, we assayed genome-wide translational changes in Drosophila. A number of nuclear encoded mitochondrial genes, including those in Complex I and IV of the electron transport chain, showed increased ribosomal loading and enhanced overall activity upon DR. We found that various mitochondrial genes possessed shorter and less structured 5'UTRs, which were important for their enhanced mRNA translation. The translational repressor 4E-BP, the eukaryotic translation initiation factor 4E binding protein, was upregulated upon DR and mediated DR dependent changes in mitochondrial activity and lifespan extension. Inhibition of individual mitochondrial subunits from Complex I and IV diminished the lifespan extension obtained upon DR, reflecting the importance of enhanced mitochondrial function during DR. Our results imply that translational regulation of nuclear-encoded mitochondrial gene expression by 4E-BP plays an important role in lifespan extension upon DR. For a video summary of this article, see the PaperFlick file with the Supplemental Data available online.
Links	PubMed PMC2759400 Online version:10.1016/j.cell.2009.07.034
Keywords	5' Untranslated Regions; Animals; Caloric Restriction; Drosophila Proteins/metabolism; Drosophila melanogaster/metabolism; Intracellular Signaling Peptides and Proteins/metabolism; Longevity; Mitochondria/metabolism; Peptide Initiation Factors/metabolism; Protein Biosynthesis; Up-Regulation
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