ArticleCell discovery2025
MAPK13 phosphorylates PHGDH and promotes its degradation via chaperone-mediated autophagy during liver injury.
Article in Cell discovery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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The trial behind it
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Who cites it
8 citing papers in PubMed.
- Floridoside as a Hinge-Targeted Inhibitor of MAPK13: Atomistic Insights from Molecular Dynamics Simulations.Marine drugs · 2026Article
- The integration of network pharmacology and multiomics reveals the mechanism by which Malus hupehensis leaves inhibit acute liver injury.BMC complementary medicine and therapies · 2026Article
- Coptidis Rhizoma Alkaloids Alleviate Acetaminophen-Induced Liver Injury by Regulating GSH Metabolism and the TNF Signaling Pathway.Antioxidants (Basel, Switzerland) · 2026Article
- Acetylation Regulates ACSL4 Degradation Through Chaperone-Mediated Autophagy to Alleviate Intervertebral Disc Degeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Infection Dynamics and Host Biomarker Identification for Spotty Liver Disease in Chickens.Veterinary sciences · 2025Article
- 3A and 2B proteins of SVA play chess game with host restriction factor DDX23 by apoptotic pathway.Journal of virology · 2025Article
- NSUN2 promotes colorectal cancer progression by stabilizing PHGDH mRNA to promote serine metabolism reprogramming.Cancer & metabolism · 2025Article
- Protein post-translational modifications in serine synthetic pathway: functions and molecular mechanisms.Cell communication and signaling : CCS · 2025Review
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Drug-induced liver injury (DILI) is the leading cause of acute liver failure and poses a significant clinical challenge in both diagnosis and treatment. Serine synthesis pathway (SSP) links glycolysis to one-carbon cycle and plays an important role in cell homeostasis by regulating substance synthesis, redox homeostasis and gene expression. However, the regulatory mechanism of SSP in DILI remains unclear. Phosphoglycerate dehydrogenase (PHGDH) is the rate-limiting enzyme in SSP. Here we show that during DILI, mitogen-activated protein kinase 13 (MAPK13) is activated and then phosphorylates PHGDH at serine 371 upon oxidative stress, which triggers PHGDH protein degradation via chaperone-mediated autophagy (CMA) pathway. PHGDH degradation suppresses SSP and glutathione production, thereby exacerbating DILI and cholestatic liver injury. Importantly, both MAPK13 inhibition and dietary serine supplementation ameliorates these liver injuries. Our finding demonstrates a unique regulatory mechanism of SSP, in which MAPK13 phosphorylates PHGDH and promotes its CMA degradation, establishes its critical role in DILI and cholestatic liver injury, and highlights the therapeutic potential of MAPK13 inhibitor or dietary serine to treat these liver injuries.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.