ArticleiScience2026
Disulfidptosis in PCOS pathogenesis: Multi-omics identification of LRPPRC as a diagnostic biomarker and therapeutic target.
Article in iScience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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8 authors.
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Abstract
Polycystic ovary syndrome (PCOS) is characterized by reproductive dysfunction, insulin resistance, oxidative stress, and metabolic abnormalities, yet the role of disulfidptosis in granulosa cell injury remains unclear. Here, integrated single-cell and bulk transcriptomic analyses identified granulosa cells as the primary disulfidptosis-associated cell type in the PCOS follicular microenvironment. Disulfidptosis-related genes, including leucine-rich pentatricopeptide repeat-containing protein (LRPPRC), NDUFS1, and OXSM, were significantly downregulated and associated with mitochondrial dysfunction and redox imbalance. A diagnostic model achieved an AUC of 0.867, while Mendelian randomization identified LRPPRC as a protective factor for PCOS. Functionally, LRPPRC deficiency under glucose deprivation induced NADPH depletion, F-actin collapse, and granulosa cell death, which was rescued by 2-mercaptoethanol but not by apoptosis, ferroptosis, or necroptosis inhibitors.
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