ArticleNature communications2015
A REDD1/TXNIP pro-oxidant complex regulates ATG4B activity to control stress-induced autophagy and sustain exercise capacity.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers.
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Who cites it
115 citing papers in PubMed, 191 citations in OpenAlex.
- Acute low-intensity cycling with blood-flow restriction has no effect on metabolic signaling in human skeletal muscle compared to traditional exercise.European journal of applied physiology · 2017Trial
- Computation-driven discovery of novel chromone derivatives for the treatment of triple-negative breast cancerActa pharmaceutica Sinica. B · 2026Article
- Hippocampal REDD1 inhibition is critical for alleviating depressive-like behaviors.Acta pharmacologica Sinica · 2026Article
- REDD1 deficiency alleviates podocyte PANoptosis and restores autophagy in diabetic kidney disease.Molecular medicine (Cambridge, Mass.) · 2026Article
- REDD1/DDIT4 counteracts endoplasmic reticulum stress-induced apoptosis by controlling the expression of death receptor TRAILR2/DR5 in cancer cells.Cell death & disease · 2026Article
- Identification and Validation of FOXK1-Related Biomarkers in Diabetic Retinopathy.International journal of general medicine · 2026Article
- Hydrogen peroxide as a multifaceted regulator of the Atg4 protease and autophagy in the pathogenic fungusFrontiers in fungal biology · 2026Article
- The Glucocorticoid Receptor Inhibits NRF2-Mediated Expression of SLC7A11.Free radical biology & medicine · 2025Article
- Adipose-derived mesenchymal stem cell therapy modulates mitochondrial function to attenuate acetaminophen-induced liver injury by DDIT4/PGC-1α axis.Stem cell research & therapy · 2025Article
- BRD4 inhibition suppresses histone H4 UFMylation to increase ferroptosis sensitivity through TXNIP.Cell death & disease · 2025Article
- The critical role of DNA damage-inducible transcript 4 (DDIT4) in stemness character of leukemia cells and leukemia initiation.Molecular oncology · 2025Article
- Targeting ATF4-DDIT4/TXNIP induced mitochondrial dysfunction and ferroptosis: ISRIB as novel therapy for septic cardiomyopathy.Journal of translational medicine · 2025Article
- Deletion of the stress response protein REDD1 prevents sodium iodate-induced RPE damage and photoreceptor loss.GeroScience · 2025Article
- Beyond Redox Regulation: Novel Roles of TXNIP in the Pathogenesis and Therapeutic Targeting of Kidney Disease.The American journal of pathology · 2025Review
- REDD1 is a determinant of the sensitivity of renal cell carcinoma cells to autophagy inhibition that can be therapeutically exploited by targeting PIM activity.Cancer letters · 2025Article
- Transcriptomic insights into early mechanisms underlying post-chikungunya chronic inflammatory joint disease.Scientific reports · 2025Article
- Increased nuclear expression of DNA damage inducible transcript 4 can serve as a potential prognostic biomarker in patients with gliomas: a study based on data mining and experimental tools.Discover oncology · 2025Article
- REDD1 attenuates cholestatic liver fibrosis and suppresses PI3K/AKT/mTOR pathway.Frontiers in medicine · 2025Article
- Review
- Resilience to diabetic retinopathy.Progress in retinal and eye research · 2024Review
55 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 7 institutions in 3 countries.
Funding
Abstract
Macroautophagy (autophagy) is a critical cellular stress response; however, the signal transduction pathways controlling autophagy induction in response to stress are poorly understood. Here we reveal a new mechanism of autophagy control whose deregulation disrupts mitochondrial integrity and energy homeostasis in vivo. Stress conditions including hypoxia and exercise induce reactive oxygen species (ROS) through upregulation of a protein complex involving REDD1, an mTORC1 inhibitor and the pro-oxidant protein TXNIP. Decreased ROS in cells and tissues lacking either REDD1 or TXNIP increases catalytic activity of the redox-sensitive ATG4B cysteine endopeptidase, leading to enhanced LC3B delipidation and failed autophagy. Conversely, REDD1/TXNIP complex expression is sufficient to induce ROS, suppress ATG4B activity and activate autophagy. In Redd1(-/-) mice, deregulated ATG4B activity and disabled autophagic flux cause accumulation of defective mitochondria, leading to impaired oxidative phosphorylation, muscle ATP depletion and poor exercise capacity. Thus, ROS regulation through REDD1/TXNIP is physiological rheostat controlling stress-induced autophagy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.