Oliver's mTOR Atlas Evidence Platform
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Pathway link 4EBP1-MITO

4E-BP1 Mitochondrial biogenesis

4E-BP1 context-dependent Mitochondrial biogenesis.

The 4E-BP branch helps set how many mitochondrial proteins get built. In mammalian cells it holds them back; in fruit flies on a restricted diet it boosts them, so the direction depends on the organism and the diet.

In mammalian cells (MOR2013) 4E-BPs repress translation of nucleus-encoded mitochondrial mRNAs, so mTORC1 raises mitochondrial output by inhibiting them; this arm is less rapamycin-sensitive than the S6K arm. In flies on dietary restriction (ZID2009) upregulated 4E-BP instead enhances translation of mitochondrial respiratory mRNAs. The sign depends on organism and nutrient state, so it is drawn as conditional.

The conditions it holds under

Scope: mammalian cells, MOR2013. The sign holds where 4E-BP represses translation of nuclear-encoded mitochondrial mRNAs (TFAM, mitochondrial ribosomal proteins), which is why this branch survives rapamycin better than the S6K arm. It does NOT hold universally across species and nutrient states: in Drosophila under dietary restriction, ZID2009 reports that 4E-BP ENHANCES mitochondrial activity, and that this is how it extends lifespan. Treat the mammalian-cell direction as scoped, not general.

Time it takes
hours
Step
indirect (through steps not drawn here)
Measured in
mammalian cells
Where in the cell
mitochondrion
Reaches people?
not tested in people
How settled
emerging, few independent studies

Studies behind it

YearEvidenceStudy
2013 M mTORC1 controls mitochondrial activity and biogenesis through 4E-BP-dependent translational regulationMOR2013 mTORC1 controls mitochondrial biogenesis and activity through 4E-BP-dependent translation.

Points the other way

YearEvidenceStudy
2009 A 4E-BP extends lifespan upon dietary restriction by enhancing mitochondrial activity in DrosophilaZID2009 Connected the dots between diet, mTOR, and lifespan. 4E-BP, an mTOR target, is upregulated on dietary restriction and here was shown to be REQUIRED for the lifespan boost, working by selectively boosting translation of mitochondrial genes. A rare case pinning a specific mTOR effector to the longevity benefit of eating less.

Who has checked this

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Curated by
Oliver Barton, with AI help for drafting; see how links are checked.

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