REDD1 (DDIT4)
Hypoxia- and glucocorticoid-induced protein that suppresses mTORC1. The route is tissue-dependent: the original cell-culture model runs through the TSC complex, but in mouse skeletal muscle in vivo REDD1-mediated inhibition is independent of TSC2/14-3-3 binding and runs through Akt and PRAS40 instead (Britto 2014, PMID 25315696). So low oxygen and weak growth-factor signals do not necessarily share a single brake.
A stress-made brake amplifier. A protein switched on by low oxygen or by stress hormones, which then puts the brakes on mTORC1. Which brake it pulls depends on the tissue: in cell culture it acts through the TSC complex, but in mouse muscle it bypasses TSC entirely and works through Akt and PRAS40.
Proposed to release TSC2 from 14-3-3 sequestration; short half-life makes it a transient rather than a maintained signal.
TL;DR. REDD1 (DDIT4) appears in 2 curated studies in Oliver's mTOR Atlas: 2 at the molecular level (cells, biochemistry, structure). No study in people is recorded for it in the Atlas yet. It has 2 interactions in the curated pathway model.
In the pathway model
| Interaction | Mechanism | Evidence | Studies |
|---|---|---|---|
| REDD1 (DDIT4) activates TSC1/TSC2 mechanism: signal-relay · this link in full · on the map table | REDD1 acts through the TSC brake, so low oxygen and low growth-factor signals end up hitting the very same switch. REDD1 works through the TSC complex, not around it - hypoxia and growth factors therefore converge on the same brake. REDD1 works through the TSC complex, not around it - hypoxia and growth factors therefore converge on the same brake. Holds under: One study in mammalian cells (BRU2004). A single study, not replicated in this corpus, and not tested in whole animals or in people. plausible in people, not shown directly · emerging, few independent studies | M | BRU2004 |
| Hypoxia activates REDD1 (DDIT4) mechanism: transcriptional · this link in full · on the map table | Low oxygen switches on the gene for REDD1 over hours - slower than AMPK. REDD1 protein is short-lived, so the signal lasts only while low oxygen keeps the gene on. Low oxygen induces REDD1 transcriptionally over hours, slower than AMPK. REDD1 protein is short-lived, so the signal lasts only as long as hypoxia keeps the gene switched on. Low oxygen induces REDD1 transcriptionally over hours, slower than AMPK. REDD1 protein is short-lived, so the signal lasts only as long as hypoxia keeps the gene switched on. Holds under: Single-study edge in this corpus. plausible in people, not shown directly · emerging, few independent studies | M | BRU2004 |
Evidence at a glance
| Evidence | What it means | Studies |
|---|---|---|
| M | Molecular — cells, biochemistry, structure | 2 |
No direct human evidence in the Atlas for this entity yet — everything below rests on animal or molecular work.
Studies
| Year | Evidence | Study |
|---|---|---|
| 2026 | M | ATF4 activates a transcriptional program that chronically suppresses mTOR activity and promotes neurodegeneration in Parkinson disease models DEMMINGS2026 Chronic integrated-stress-response signalling through ATF4 coordinately upregulates SESN2, DDIT4 and Trib3, which together suppress BOTH mTORC1 and mTORC2; this sustained mTOR inhibition drives dopaminergic neuron death via the pro-apoptotic BCL-2 family protein PUMA. Defines a maladaptive ISR/ATF4-to-mTOR axis in Parkinson disease models — a case where LESS mTOR activity is harmful, opposite to the usual longevity framing. |
| 2004 | M | Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex BRU2004 Hypoxia inhibits mTOR via REDD1-dependent activation of the TSC1/2 complex. |
Related entities
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