| Title | 4E-BP extends lifespan upon dietary restriction by enhancing mitochondrial activity in Drosophila. | | Author(s) | Zid BM, Rogers AN, Katewa SD, Vargas MA, Kolipinski MC, Lu TA, Benzer S, Kapahi P | | Institution | California Institute of Technology, Pasadena, CA 91125, USA. | | Source | Cell 2009 Oct 2; 139(1):149-60. | | MeSH | 5' Untranslated Regions
Animals
Caloric Restriction
Drosophila Proteins
Drosophila melanogaster
Intracellular Signaling Peptides and Proteins
Longevity
Mitochondria
Peptide Initiation Factors
Protein Biosynthesis
Up-Regulation
| | 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. | | Language | eng | | Pub Type(s) | Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
| | PubMed ID | 19804760 |
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