ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2010
Palmitoylation of ketogenic enzyme HMGCS2 enhances its interaction with PPARalpha and transcription at the Hmgcs2 PPRE.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 83 citations in OpenAlex.
- Perilipin 2 drives cisplatin-induced acute kidney injury in young but not aged kidneys.American journal of physiology. Renal physiology · 2026Article
- HMGCS2 Palmitoylation Promotes Diabetes-Induced Erectile Dysfunction Through PPARα-Mediated Macrophage Extracellular Trap Formation.Journal of inflammation research · 2026Article
- Recent advances in S-palmitoylation and its emerging roles in human diseases.Journal of hematology & oncology · 2025Review
- Palmitoylation: an emerging therapeutic target bridging physiology and disease.Cellular & molecular biology letters · 2025Review
- Not Just an Alternative Energy Source: Diverse Biological Functions of Ketone Bodies and Relevance of HMGCS2 to Health and Disease.Biomolecules · 2025Review
- Maladaptive Peripheral Ketogenesis in Schwann Cells Mediated by CBAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Discovery of PPAR Alpha Lipid Pathway Modulators That Do Not Bind Directly to the Receptor as Potential Anti-Cancer Compounds.International journal of molecular sciences · 2025Article
- Preliminary investigation on the establishment of a new meibomian gland obstruction model and gene expression.Scientific reports · 2024Article
- Restoration of HMGCS2-mediated ketogenesis alleviates tacrolimus-induced hepatic lipid metabolism disorder.Acta pharmacologica Sinica · 2024Article
- BET inhibition decreases HMGCS2 and sensitizes resistant pancreatic tumors to gemcitabine.Cancer letters · 2024Article
- Downregulation of HMGCS2 mediated AECIIs lipid metabolic alteration promotes pulmonary fibrosis by activating fibroblasts.Respiratory research · 2024Article
- SLC16a6, mTORC1, and Autophagy Regulate Ketone Body Excretion in the Intestinal Cells.Biology · 2023Article
- Post-translational palmitoylation of metabolic proteins.Frontiers in physiology · 2023Review
- The proteomic effects of ketone bodies: implications for proteostasis and brain proteinopathies.Frontiers in molecular neuroscience · 2023Review
- Full-length huntingtin is palmitoylated at multiple sites and post-translationally myristoylated following caspase-cleavage.Frontiers in physiology · 2023Article
- Metabolic Changes Associated With Cardiomyocyte Dedifferentiation Enable Adult Mammalian Cardiac Regeneration.Circulation · 2022Article
- Hmgcs2-mediated ketogenesis modulates high-fat diet-induced hepatosteatosis.Molecular metabolism · 2022Article
- Emerging Role of Hepatic Ketogenesis in Fatty Liver Disease.Frontiers in physiology · 2022Review
- Transcriptome Analysis of Bovine Rumen Tissue in Three Developmental Stages.Frontiers in genetics · 2022Article
- Glioma Stem-Like Cells and Metabolism: Potential for Novel Therapeutic Strategies.Frontiers in oncology · 2021Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Excessive liver production of ketone bodies is one of many metabolic complications that can arise from diabetes, and in severe untreated cases, it can result in ketoacidosis, coma, and death. Mitochondrial HMG-CoA synthase (HMGCS2), the rate-limiting enzyme in ketogenesis, has been shown to interact with PPARalpha and act as a coactivator to up-regulate transcription from the PPRE of its own gene. Although protein palmitoylation is typically a cytosolic process that promotes membrane association, we recently identified 21 palmitoylated proteins in rat liver mitochondria, including HMGCS2. Herein, our data support a mechanism whereby palmitate is first added onto HMGCS2 active site Cys166 and then transacylated to Cys305. Palmitoylation promotes the HMGCS2/PPARalpha interaction, resulting in transcriptional activation from the Hmgcs2 PPRE. These results, together with the fact that 8 of the 21 palmitoylated mitochondrial proteins that we previously identified have nuclear receptor interacting motifs, demonstrate a novel--and perhaps ubiquitous--role for palmitoylation as a modulator of transcription.
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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.