Redox activation of ATG5 licenses autophagy upon nutrient restriction

Shin S, Korobkina ED, Lennicke C, Burger N, Zhang B, Xiao H, Wang Y, Petrocelli JJ, Wei SM, Wood D, Lei Y, …, Chouchani ET · 2026 · bioRxiv · Atlas ID SHI2026

What this study shows

Dietary restriction selectively oxidizes a specific, tissue-resolved set of cysteines rather than oxidizing the proteome broadly. One of the most strongly oxidized is Cys19 on the core autophagy protein ATG5; this oxidation is required for ATG5 to bind ATG10 and form the ATG5-ATG12 conjugate that lipidates LC3B and builds the autophagosome. In mice lacking this redox switch, nutrient restriction fails to trigger autophagy, causing severe tissue pathology and early death -- a single oxidized cysteine gates the autophagic response to fasting.

Abstract

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Dietary restriction (DR) protects against metabolic disease, extends lifespan, and is associated with remodeling of tissue reactive oxygen species (ROS). ROS control biological adaptation through reversible oxidation of protein cysteines, yet the targets of DR-initiated redox signaling are unknown. Here we generate OxiDR, a tissue-resolved atlas of the cysteine redox proteome that quantifies oxidation state under DR.

Read the full abstract on PubMed →

At a glance

Evidence type	PP Preprint, not peer-reviewed This is a preprint, not yet peer-reviewed -- treat its findings as provisional until formal publication. Preprints carry their own marker because peer-review status is a different question from which system was studied.
Study type	Preprint
Model system	Human cell lines and mice; tissue-resolved cysteine redox proteomics (OxiDR atlas) under dietary restriction
Journal	bioRxiv
Year	2026
Peer reviewed	No
Record last updated	2026-10-01
Source	DOI 10.64898/2026.09.23.753803 · PMID 42818375 · Free full text (PMC13622291)

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

Intervention	Dietary restriction; ATG5 Cys19 redox-dead mutation
Target	ATG5 Cys19 oxidation; autophagy
Model	Human cell lines and mice
Effect	Oxidation of ATG5 Cys19 was required for nutrient-restriction-induced autophagy; mice lacking it developed tissue pathology and early death.

In the Atlas

Cite this paper

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Shin, S., Korobkina, E. D., Lennicke, C., Burger, N., Zhang, B., Xiao, H., Wang, Y., Petrocelli, J. J., Wei, S. M., Wood, D., Lei, Y., Zhang, X., Perez-Matos, M. C., Sharif, M. A., Zhang, J., Cochemé, H. M., Mair, W. B., & Chouchani, E. T. (2026). Redox activation of ATG5 licenses autophagy upon nutrient restriction. bioRxiv. https://doi.org/10.64898/2026.09.23.753803

@article{SHI2026,
  author       = {Shin, S. and Korobkina, E. D. and Lennicke, C. and Burger, N. and Zhang, B. and Xiao, H. and Wang, Y. and Petrocelli, J. J. and Wei, S. M. and Wood, D. and Lei, Y. and Zhang, X. and Perez-Matos, M. C. and Sharif, M. A. and Zhang, J. and Cochemé, H. M. and Mair, W. B. and Chouchani, E. T.},
  title        = {{Redox activation of ATG5 licenses autophagy upon nutrient restriction}},
  journal      = {bioRxiv},
  year         = {2026},
  doi          = {10.64898/2026.09.23.753803},
  note         = {PMID: 42818375},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record SHI2026) [Data set]. https://mtor-atlas.org/study/SHI2026/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_SHI2026,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record SHI2026},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/SHI2026/},
  doi          = {10.5281/zenodo.22059963}
}

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