ArticleInternational journal of biological sciences2026
Curcumol Induces Necroptosis of Hepatic Stellate Cells by Targeting KAT8 to Suppress HK2 Lactylation and Promote HUWE1-Dependent Ubiquitination.
Article in International journal of biological sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Lactylation in gastric cancer: From mechanisms to clinical applications (Review).Molecular medicine reports · 2026Review
- Regulatory complexity and therapeutic targeting of the necroptosis network.Frontiers in immunology · 2026Review
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17 authors.
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Abstract
Liver fibrosis is a pathological outcome of chronic liver injury and is primarily driven by the continuous activation of hepatic stellate cells (HSCs). During activation, HSCs depend on aerobic glycolysis to maintain their fibrogenic characteristics, suggesting that metabolic reprogramming could serve as an effective therapeutic approach. In this study, we demonstrate that Curcumol, a natural compound derived from plants in the Zingiberaceae family, selectively removes activated HSCs by interfering with the lactate-KAT8-HK2 regulatory pathway. In HSCs, lactate produced through glycolysis activates the acetyltransferase KAT8, which catalyzes K346 lactylation of hexokinase 2 (HK2). This modification creates a positive feedback mechanism that stabilizes HK2. Curcumol acts directly on KAT8, inhibiting HK2 lactylation and promoting HUWE1-mediated ubiquitination and degradation of HK2. The resulting loss of HK2 removes its inhibitory influence on RIPK1 ubiquitination, leading to activation of the RIPK1/RIPK3/MLKL signaling pathway and triggering necroptosis.
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