Chen, Xu, Zhou, Wu et al. report that a citric acid cycle enzyme OGDH regulates METTL3 succinylation and its activation as an m6A reader, thereby modulating NRF2 translation, disulfidptosis evasion an...

Purpose Glucose starvation induces the accumulation of disulfides and F-actin collapse in cells with high expression of SLC7A11, a phenomenon termed disulfidptosis. This study aimed to confirm the exi...

Wan, J. Shi, M. Shi, Huang et al. report a role for lactate dehydrogenase B in regulating CD8+ T cell disulfidptosis and exhaustion through the activity of glucose-6-phosphate dehydrogenase, thereby i...

Nature Cell Biology - Douglas et al. study the E3 ligase HOIL-1, mutated in patients with a type of myopathy. Mutant HOIL-1 influences the sensitivity to disulfidptosis initiated by...

Douglas et al. study the E3 ligase HOIL-1, mutated in patients with a type of myopathy. Mutant HOIL-1 influences the sensitivity to disulfidptosis initiated by ZAKα–ATF4 in glucose starvation and inte...

Disulfidptosis, a form of cell death driven by accumulation of abnormal disulfide bonds, was first used to describe death induced by glucose deprivation in SLC7A11-high cancer cells. A study now ident...

Douglas et al. study the E3 ligase HOIL-1, mutated in patients with a type of myopathy. Mutant HOIL-1 influences the sensitivity to disulfidptosis initiated by ZAKα–ATF4 in glucose starvation and inte...

Although disulfide stress in cancer cells under glucose starvation is known to trigger disulfidptosis, its role in the tumour microenvironment has remained unclear. A recent study in Nature Cell Biology reveals that in intratumoural CD8+ T cells, disulfidptosis promotes T cell exhaustion and thereby limits antitumour imunity.

Douglas et al. study the E3 ligase HOIL-1, mutated in patients with a type of myopathy. Mutant HOIL-1 influences the sensitivity to disulfidptosis initiated by ZAKα–ATF4 in glucose starvation and inte...

Cell Death & Differentiation - Ribosome stress meets disulfidptosis: HOIL-1 safeguards cell fate during nutrient deprivation

Cell Death & Differentiation - Ribosome stress meets disulfidptosis: HOIL-1 safeguards cell fate during nutrient deprivation

The aberrant accumulation of intracellular disulfides promotes cancer cell disulfidptosis; however, how disulfide stress influences tumour-infiltrating CD8+ T cell function remains unknown. Here we demonstrate that lactate dehydrogenase B (LDHB) facilitates intratumoural CD8+ T cell disulfidptosis and exhaustion, leading to impaired antitumour immunity. SLC7A11-mediated cystine uptake by CD8+ T cells induces disulfidptosis, which plays critical roles in the development of exhausted CD8+ T cells. LDHB restricts glucose-6-phosphate dehydrogenase (G6PD) activity in exhausted CD8+ T cells by interacting with G6PD, causing NADPH depletion and consequently triggering disulfidptosis. Accordingly, the loss of LDHB in T cells prevents disulfidptosis-dependent CD8+ T cell exhaustion and improves antitumour immunity. Mechanistically, STAT3 directs LDHB expression to limit G6PD activity and mediate disulfidptosis in exhausted CD8+ T cells. Our results highlight the distinct roles of disulfidptosis

Wan, J. Shi, M. Shi, Huang et al. report a role for lactate dehydrogenase B in regulating CD8+ T cell disulfidptosis and exhaustion through the activity of glucose-6-phosphate dehydrogenase, thereby i...

Nature Cell Biology - Douglas et al. study the E3 ligase HOIL-1, mutated in patients with a type of myopathy. Mutant HOIL-1 influences the sensitivity to disulfidptosis initiated by...

Nature Reviews Cancer, Published online: 02 July 2025; doi:10.1038/s41568-025-00849-0Although disulfide stress in cancer cells under glucose starvation is known to trigger disulfidptosis, its role in the tumour microenvironment has remained unclear. A recent study in Nature Cell Biology reveals that in intratumoural CD8+ T cells, disulfidptosis promotes T cell exhaustion and thereby limits antitumour imunity.

Wan, J. Shi, M. Shi, Huang et al. report a role for lactate dehydrogenase B in regulating CD8+ T cell disulfidptosis and exhaustion through the activity of glucose-6-phosphate dehydrogenase, thereby i...

Read the full paper: Quantification of Single‐Cell Cysteine Using an Electrochemical Nanosensor for Predicting Tumor Disulfidptosis Susceptibility

Nature Reviews Molecular Cell Biology, Published online: 22 August 2025; doi:10.1038/s41580-025-00888-3In this Comment, Boyi Gan discusses disulfidptosis, a newly identified, redox-driven cell death pathway triggered by disulfide stress, and highlights its therapeutic potential while underscoring gaps in mechanistic understanding and key challenges for future research.

Nature Reviews Molecular Cell Biology, Published online: 22 August 2025; doi:10.1038/s41580-025-00888-3In this Comment, Boyi Gan discusses disulfidptosis, a newly identified, redox-driven cell death pathway triggered by disulfide stress, and highlights its therapeutic potential while underscoring gaps in mechanistic understanding and key challenges for future research.