ArticleJournal of advanced research2025
NSP6 regulates calcium overload-induced autophagic cell death and is regulated by KLHL22-mediated ubiquitination.
Article in Journal of advanced research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Review
- Biological significance, molecular mechanisms and clinical potential of EI24 in cancer.Chinese medical journal · 2026Review
- Exosomes in inflammatory tissue injury: key pathogenic factors and promising therapeutic agents.Frontiers in immunology · 2026Review
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a substantial global threat. SARS-CoV-2 nonstructural proteins (NSPs) are essential for impeding the host replication mechanism while also assisting in the production and organization of new viral components. However, NSPs are not incorporated into viral particles, and their subsequent fate within host cells remains poorly understood. Additionally, their role in viral pathogenesis requires further investigation.
objectivesThis study aimed to discover the ultimate fate of NSP6 in host cells and to elucidate its role in viral pathogenesis.
methodsWe investigated the effects of NSP6 on cell death and explored the underlying mechanism; moreover, we examined the degradation mechanism of NSP6 in human cells, along with analysing its correlation with coronavirus disease 2019 (COVID-19) severity in patient peripheral blood mononuclear cells (PBMCs).
resultsNSP6 was demonstrated to induce cell death. Specifically, NSP6 interacted with EI24 autophagy-associated transmembrane protein (EI24) to increase intracellular Ca
conclusionThis study reveals that KLHL22-mediated ubiquitination controls NSP6 stability and that NSP6 induces autophagic cell death via calcium overload, highlighting its cytotoxic role and suggesting therapeutic strategies that target calcium signaling or promote NSP6 degradation as potential interventions against COVID-19.
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