Amino acid homeostasis by CORVET/HOPS: A metabolic and stress resilience checkpoint for T cells

Wang J, Ni Z, Zhang Xinxin, He L, Cheng X, Huang L, Ye H, Li P, Zhao TJ, Du X · 2026 · Proceedings of the National Academy of Sciences · Atlas ID WANG2026

What this study shows

Identifies the CORVET and HOPS endolysosomal tethering complexes as upstream suppliers of intracellular amino acids in activated T cells, acquired via macropinocytosis. Loss of the core subunits VPS18 or VPS11 starves the cell of amino acids, switches on the integrated stress response and shuts down mTORC1; enforced mTORC1 activity rescues the proliferative defect while BIM deletion rescues survival, separating the two failure modes. Places vesicular nutrient acquisition upstream of the canonical lysosomal amino-acid-sensing arm of mTORC1.

Abstract

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Amino acid sufficiency is critical for T cell metabolic reprogramming, yet how T cells maintain amino acid homeostasis remains poorly defined. Here, we identify the CORVET and HOPS (CORVET/HOPS) tethering complexes as essential upstream regulators. In activated T cells, they sustain intracellular amino acid levels by promoting macropinocytosis to acquire extracellular nutrients. This function enables dual signaling outcomes: suppression of the integrated stress response (ISR) and activation of mTORC1, which together license metabolic plasticity and effector function.

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At a glance

Evidence type	M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Mouse T cells (conditional VPS18 / VPS11 knockout, in vitro and in vivo)) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is.
Study type	5 - Mechanistic / In Vitro
Model system	Mouse T cells (conditional VPS18 / VPS11 knockout, in vitro and in vivo)
Journal	Proceedings of the National Academy of Sciences
Year	2026
Peer reviewed	Yes
Record last updated	2026-08-22
Source	DOI 10.1073/pnas.2601318123 · PMID 42647134

Extracted findings

Intervention	Genetic ablation of CORVET/HOPS subunits VPS18 or VPS11; BIM deletion; enforced mTORC1 activity
Target	CORVET/HOPS tethering complexes; mTORC1; integrated stress response
Model	Mouse (T cells, in vitro and in vivo)
Effect	CORVET/HOPS loss causes amino acid scarcity, ISR activation and mTORC1 failure, abrogating T cell immunity

Cite this paper

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Wang, J., Ni, Z., Zhang Xinxin, He, L., Cheng, X., Huang, L., Ye, H., Li, P., Zhao, T. J., & Du, X. (2026). Amino acid homeostasis by CORVET/HOPS: A metabolic and stress resilience checkpoint for T cells. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.2601318123

@article{WANG2026,
  author       = {Wang, J. and Ni, Z. and Zhang Xinxin and He, L. and Cheng, X. and Huang, L. and Ye, H. and Li, P. and Zhao, T. J. and Du, X.},
  title        = {{Amino acid homeostasis by CORVET/HOPS: A metabolic and stress resilience checkpoint for T cells}},
  journal      = {Proceedings of the National Academy of Sciences},
  year         = {2026},
  doi          = {10.1073/pnas.2601318123},
  note         = {PMID: 42647134},
}

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 WANG2026) [Data set]. https://mtor-atlas.org/study/WANG2026/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_WANG2026,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record WANG2026},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/WANG2026/},
  doi          = {10.5281/zenodo.22059963}
}