Research article summary (published 30 Sep 2009):

4E-BP extends lifespan upon dietary restriction by enhancing mitochondrial activity in Drosophila.

Full 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.

Author information

Author/s: Zid, Brian M (BM); Rogers, Aric N (AN); Katewa, Subhash D (SD); Vargas, Misha A (MA); Kolipinski, Marysia C (MC); Lu, Tony Au (TA); Benzer, Seymour (S); Kapahi, Pankaj (P);

Affiliation: California Institute of Technology, Pasadena, CA 91125, USA.

Grants: 1R21 AG 028241-01 (Agency:NIA NIH HHS) ; RL1A AG 032113 (Agency:NIA NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Cell (Cell), published in United States. (Language: eng)

Reference: 2009-Oct; vol 139 (issue 1) : pp 149-60

Dates: Created 2009/10/06; Completed 2009/10/27;

PMID: 19804760, status: MEDLINE (last retrieval date: 10/27/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

5' Untranslated Regions Animals Caloric Restriction Drosophila Proteins - metabolism Drosophila melanogaster - metabolism Intracellular Signaling Peptides and Proteins - metabolism

Intracellular Signaling Peptides and Proteins - metabolism Longevity Mitochondria - metabolism Peptide Initiation Factors - metabolism Protein Biosynthesis Up-Regulation

Associated Chemicals: 5' Untranslated Regions (0) ; Drosophila Proteins (0) ; Intracellular Signaling Peptides and Proteins (0) ; Peptide Initiation Factors (0) ; Thor protein, Drosophila (0)

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