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

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.

journal_name

Cell

journal_title

Cell

authors

Zid BM,Rogers AN,Katewa SD,Vargas MA,Kolipinski MC,Lu TA,Benzer S,Kapahi P

doi

10.1016/j.cell.2009.07.034

subject

Has Abstract

pub_date

2009-10-02 00:00:00

pages

149-60

issue

1

eissn

0092-8674

issn

1097-4172

pii

S0092-8674(09)00914-3

journal_volume

139

pub_type

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